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Álvarez J, Parody N, Calzada D, Aranda T, Renshaw A, Serna S, Reichardt N, Beitia JM, González-de-Olano D, Dominguez-Ortega J, Carnés J. Correlation Between N-Glycan GnGnXF3 and the Allergic Immune Response Against Juniperus ashei Pollen. Allergy 2025. [PMID: 39912313 DOI: 10.1111/all.16475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 12/20/2024] [Accepted: 01/02/2025] [Indexed: 02/07/2025]
Abstract
BACKGROUND Cupressaceae pollen increasingly causes respiratory allergies worldwide. Carbohydrates are abundant in extracts of these pollens, and the associated allergens are highly glycosylated. However, the contribution of saccharides to the allergenicity of these species remains unknown. METHODS Juniperus ashei pollen extract was deglycosylated and characterised using SDS-PAGE and immunoblotting. Additionally, N- and O-glycans were purified from the extract, identified, used as inhibitors in IgE-immunoblotting and further analysed via basophil activation tests. The interactions between IgE and J. ashei glycans were analysed using a glycan array. Purified Jun a 1 was treated with β-N-acetylglucosaminidase S and analysed using immunoblotting. The native pollen extract was used to immunise rabbits, and the IgG response was analysed using ELISA and glycan array. RESULTS Deglycosylation of J. ashei proteins abolished the interaction between IgE and allergens. This effect primarily depends on N-glycans. Purified N-glycans triggered basophil activation in some patients. A biantennary N-glycan with terminal GlcNAc, β-1,2 xylose and core α-1,3 fucose (GnGnXF3) was the most abundant glycan identified. The glycan array confirmed its interaction with IgE. The contribution of terminal N-acetylglucosamines (GlcNAc) to IgE-Jun a 1 interaction was validated. Moreover, effective immunisation of rabbits with the native extract confirmed the immunogenicity of their N-glycans. CONCLUSIONS The IgE-J. ashei allergen interaction is broadly controlled through N-glycans different from MUXF3. GnGnXF3 exerts an immunogenic effect in humans and rabbits; terminal GlcNAc residues influence its recognition by IgE. These discoveries reinforce the role of N-glycans in the allergic response to J. ashei.
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Affiliation(s)
- Javier Álvarez
- R&D Unit. Allergy & Immunology, LETI Pharma SLU, Madrid, Spain
| | - Nuria Parody
- R&D Unit. Allergy & Immunology, LETI Pharma SLU, Madrid, Spain
| | - David Calzada
- R&D Unit. Allergy & Immunology, LETI Pharma SLU, Madrid, Spain
| | - Tamara Aranda
- R&D Unit. Allergy & Immunology, LETI Pharma SLU, Madrid, Spain
| | - Ana Renshaw
- Centro de Biología Molecular Severo Ochoa, Madrid, Spain
| | - Sonia Serna
- Glycotechnology Group, CICbiomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, Spain
| | - Niels Reichardt
- Glycotechnology Group, CICbiomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, Spain
- Asparia Glycomics, San Sebastian, Spain
| | | | | | - Javier Dominguez-Ortega
- Department of Allergy, Hospital Universitario La Paz. Institute for Health Research (IdiPAZ), Madrid, Spain
| | - Jerónimo Carnés
- R&D Unit. Allergy & Immunology, LETI Pharma SLU, Madrid, Spain
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Hou YB, Sun JL. Common pollen and related allergen components in patients with allergic diseases in the Beijing area. FRONTIERS IN ALLERGY 2024; 5:1478392. [PMID: 39640430 PMCID: PMC11617527 DOI: 10.3389/falgy.2024.1478392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 10/30/2024] [Indexed: 12/07/2024] Open
Abstract
Background Pollen is the most common outdoor allergen that causes allergic rhinitis and asthma, which seriously affects patient quality of life and extensive cross-reactivity occurs between pollen allergens. Methods The study enrolled 84 patients with respiratory allergies and at least one pollen allergy who visited the clinic. Specific-IgE was detected via immunoblotting in the sera of patients with positive respiratory allergies to pollen. IgE of the components and cross-reactive carbohydrate determinants (CCD) were evaluated using a fluorescence-encoded microsphere assay. Results Our results suggest that Artemisia absinthium, Artemisia vulgaris, Humulus scandens, Amaranthus, Parietaria micrantha allergies are most common in the northern region, and that weed pollen remains the major pollen allergen in the northern region. Among the different age groups, the positive rate of Platanus pollen allergens was significantly higher in patients ≤18 years of age than in those aged >18 years (55.56% vs. 9.17%, χ² = 0.55, p < 0.027). Patients with allergic rhinitis and asthma had an increased positive rate for Betula pollen allergen (20.00% vs. 37.93 χ² = 7.87, p = 0.005) and Platanus pollen allergen (27.27% vs. 51.72%, χ² = 11.05, p = 0.0008) than those with allergic rhinitis alone, although the allergen positivity rate did not significantly differ between sexes. In addition, the positivity of sIgE of allergen components did not reveal a correlation with clinical symptoms and anti-CCD IgE positivity was 1.19% (1/84) among all patients. Conclusion The study found the distribution characteristics of common pollen allergens in Beijing among patients of different ages and genders and with different allergic diseases, as well as the relationship between pollen allergen components and symptoms. The positivity rate of CCD for respiratory allergic diseases in Beijing was not high as well.
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Affiliation(s)
- Yi-Bo Hou
- State Key Laboratory of Complex Severe and Rare Diseases, Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Diseases, Allergy Department, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin-Lu Sun
- State Key Laboratory of Complex Severe and Rare Diseases, Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Diseases, Allergy Department, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Grosch J, Eberlein B, Waldherr S, Pascal M, Dorn B, San Bartolomé C, De La Roca Pinzón F, Schiener M, Darsow U, Biedermann T, Lidholm J, Bilò MB, Jakob T, Schmidt-Weber CB, Blank S. Comparative Assessment of the Allergenicity of Hyaluronidases from Polistes dominula (Pol d 2), Vespula vulgaris (Ves v 2), and Apis mellifera Venom (Api m 2). Toxins (Basel) 2024; 16:498. [PMID: 39591253 PMCID: PMC11598713 DOI: 10.3390/toxins16110498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 11/09/2024] [Accepted: 11/16/2024] [Indexed: 11/28/2024] Open
Abstract
Sensitization to cross-reactive allergens complicates identifying the culprit insect in Hymenoptera venom allergy via diagnostic tests. This study evaluates sensitization to hyaluronidases (Api m 2 from honey bee (Apis mellifera) venom, HBV; Pol d 2 from European paper wasp (Polistes dominula) venom, PDV; and Ves v 2.0101 and Ves v 2.0201 from yellow jacket (Vespula vulgaris) venom, YJV) and their cross-reactivity in allergic patients from Italy, Spain, and Germany using ImmunoCAPs, ELISA, and basophil activation tests. Sensitization rates were 45% for Api m 2 in HBV-allergic subjects, 25% for Pol d 2 in PDV-allergic individuals, and 20% and 10% for Ves v 2.0201 and Ves v 2.0101 in YJV-allergic patients, respectively. Patients primarily sensitized to Api m 2 showed minimal cross-reactivity to vespid hyaluronidases, whereas those primarily sensitized to Pol d 2 or Ves v 2.0201 exhibited IgE reactivity to Api m 2. Neither Pol d 2 nor Ves v 2.0201 triggered basophil activation. Cross-reactivity of Api m 2, Pol d 2, and Ves v 2.0201 depends on the primary sensitizing venom. Sensitization to Pol d 2 and Ves v 2.0201 remains below 25%, yet these patients may exhibit cross-reactivity to Api m 2. Conversely, HBV-allergic patients sensitized to Api m 2 show minimal reactivity to Pol d 2 or Ves v 2.0201.
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Affiliation(s)
- Johannes Grosch
- Center of Allergy and Environment (ZAUM), Technical University of Munich, School of Medicine and Health & Helmholtz Munich, German Research Center for Environmental Health, 85764 Munich, Germany; (J.G.); (M.S.); (C.B.S.-W.)
| | - Bernadette Eberlein
- Department of Dermatology and Allergy Biederstein, School of Medicine and Health, Technical University of Munich, 80802 Munich, Germany; (B.E.); (U.D.); (T.B.)
| | - Sebastian Waldherr
- Department of Dermatology and Allergy Biederstein, School of Medicine and Health, Technical University of Munich, 80802 Munich, Germany; (B.E.); (U.D.); (T.B.)
| | - Mariona Pascal
- Immunology Department, CDB Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08007 Barcelona, Spain;
- Spanish Network for Allergy-RETIC de Asma, Reacciones Adversas y Alérgicas (ARADYAL), 28040 Madrid, Spain
| | - Britta Dorn
- Experimental Dermatology and Allergy Research Group, Department of Dermatology and Allergology, Justus-Liebig-University Gießen, 35392 Gießen, Germany; (B.D.); (T.J.)
| | - Clara San Bartolomé
- Immunology Department, CDB Hospital Clinic de Barcelona, Universitat de Barcelona, 08007 Barcelona, Spain;
| | | | - Maximilian Schiener
- Center of Allergy and Environment (ZAUM), Technical University of Munich, School of Medicine and Health & Helmholtz Munich, German Research Center for Environmental Health, 85764 Munich, Germany; (J.G.); (M.S.); (C.B.S.-W.)
| | - Ulf Darsow
- Department of Dermatology and Allergy Biederstein, School of Medicine and Health, Technical University of Munich, 80802 Munich, Germany; (B.E.); (U.D.); (T.B.)
| | - Tilo Biedermann
- Department of Dermatology and Allergy Biederstein, School of Medicine and Health, Technical University of Munich, 80802 Munich, Germany; (B.E.); (U.D.); (T.B.)
| | | | - Maria Beatrice Bilò
- Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60121 Ancona, Italy;
- Allergy Unit, Department of Internal Medicine, University Hospital of Ancona, 60126 Ancona, Italy
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale di Riposo e Cura per Anziani (INCRA), 60121 Ancona, Italy
| | - Thilo Jakob
- Experimental Dermatology and Allergy Research Group, Department of Dermatology and Allergology, Justus-Liebig-University Gießen, 35392 Gießen, Germany; (B.D.); (T.J.)
| | - Carsten B. Schmidt-Weber
- Center of Allergy and Environment (ZAUM), Technical University of Munich, School of Medicine and Health & Helmholtz Munich, German Research Center for Environmental Health, 85764 Munich, Germany; (J.G.); (M.S.); (C.B.S.-W.)
| | - Simon Blank
- Center of Allergy and Environment (ZAUM), Technical University of Munich, School of Medicine and Health & Helmholtz Munich, German Research Center for Environmental Health, 85764 Munich, Germany; (J.G.); (M.S.); (C.B.S.-W.)
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Olivry T, Fontao AM, Aumayr M, Ivanovova NP, Mitterer G, Harwanegg C. Validation of a Multiplex Molecular Macroarray for the Determination of Allergen-Specific IgE Sensitizations in Dogs. Vet Sci 2024; 11:482. [PMID: 39453074 PMCID: PMC11512340 DOI: 10.3390/vetsci11100482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 09/18/2024] [Accepted: 10/04/2024] [Indexed: 10/26/2024] Open
Abstract
Detecting IgE sensitizations in the serum of allergic dogs is commonly performed using allergen extracts, but these are difficult to standardize. This article details the development and validation of the Pet Allergy Xplorer (PAX; Nextmune, Stockholm, Sweden), the first multiplex macroarray for the detection of IgE sensitization in dogs using allergen extracts and molecular components; the PAX is derived from the Allergy Xplorer (ALEX2; MacroArray Diagnostics, Vienna, Austria). The selection of allergens, cartridge processing, strategy for identifying and blocking IgE directed against cross-reactive carbohydrate determinants (CCDs), and the method used for determining the positivity threshold are described. The validation of the PAX included evaluations of the specificity of its anti-IgE monoclonal antibody, specificity of IgE binding to target allergens, assay precision, and internal consistency. Additionally, the influence of possible confounding factors, such as sample type, the influence of hemolysis, lipemia, bilirubinemia, and elevated CCD-IgE, was tested. Finally, the sensitization rates of 23,858 European dogs to 145 environmental and Hymenoptera venom allergens were summarized. The PAX is accurate and reproducible and has a unique CCD-detection and blocking strategy; its molecular allergens offer a unique window on allergen cross-reactivity.
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Affiliation(s)
- Thierry Olivry
- Nextmune AB, Riddargatan 19, SE-114-56 Stockholm, Sweden
| | | | - Martina Aumayr
- MacroArray Diagnostics, Lemböckgasse 59, 1230 Vienna, Austria; (M.A.); (N.P.I.); (G.M.); (C.H.)
| | | | - Georg Mitterer
- MacroArray Diagnostics, Lemböckgasse 59, 1230 Vienna, Austria; (M.A.); (N.P.I.); (G.M.); (C.H.)
| | - Christian Harwanegg
- MacroArray Diagnostics, Lemböckgasse 59, 1230 Vienna, Austria; (M.A.); (N.P.I.); (G.M.); (C.H.)
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Ebo DG, Toscano A, Rihs HP, Mertens C, Sabato V, Elst J, Beyens M, Hagendorens MM, Van Houdt M, Van Gasse AL. IgE-Mediated Cannabis Allergy and Cross-Reactivity Syndromes: A Roadmap for Correct Diagnosis and Management. Curr Allergy Asthma Rep 2024; 24:407-414. [PMID: 38990404 DOI: 10.1007/s11882-024-01159-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2024] [Indexed: 07/12/2024]
Abstract
PURPOSE OF THE REVIEW With increased access and decriminalization of cannabis use, cases of IgE-dependent cannabis allergy (CA) and cross-reactivity syndromes have been increasingly reported. However, the exact prevalence of cannabis allergy and associated cross-reactive food syndromes (CAFS) remains unknown and is likely to be underestimated due to a lack of awareness and insufficient knowledge of the subject among health care professionals. Therefore, this practical roadmap aims to familiarize the reader with the early recognition and correct management of IgE-dependent cannabis-related allergies. In order to understand the mechanisms underlying these cross-reactivity syndromes and to enable personalized diagnosis and management, special attention is given to the molecular diagnosis of cannabis-related allergies. RECENT FINDINGS The predominant signs and symptoms of CA are rhinoconjunctivitis and contact urticaria/angioedema. However, CA can also present as a life-threatening condition. In addition, many patients with CA also have distinct cross-reactivity syndromes, mainly involving fruits, vegetables, nuts and cereals. At present, five allergenic components of Cannabis sativa (Can s); Can s 2 (profilin), Can s 3 (a non-specific lipid protein), Can s 4 (oxygen-evolving enhancer protein 2 oxygen), Can s 5 (the Bet v 1 homologue) and Can s 7 (thaumatin-like protein) have been characterized and indexed in the WHO International Union of Immunological Sciences (IUIS) allergen database. However, neither of them is currently readily available for diagnosis, which generally starts by testing crude extracts of native allergens. The road to a clear understanding of CA and the associated cross-reactive food syndromes (CAFS) is still long and winding, but well worth further exploration.
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Affiliation(s)
- Didier G Ebo
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Campus Drie Eiken T5.95 Universiteitsplein 1, Antwerp, 2610, Belgium.
- Department of Immunology and Allergology, AZ Jan Palfijn Gent, Ghent, Belgium.
- Antwerp (Belgium) and Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium.
| | - Alessandro Toscano
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Campus Drie Eiken T5.95 Universiteitsplein 1, Antwerp, 2610, Belgium
- Antwerp (Belgium) and Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
| | - Hans-Peter Rihs
- PA-Institute for Prevention and Occupational Medicine, German Social Accident Insurance, Ruhr-University Bochum, Bochum, Germany
| | - Christel Mertens
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Campus Drie Eiken T5.95 Universiteitsplein 1, Antwerp, 2610, Belgium
- Antwerp (Belgium) and Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
| | - Vito Sabato
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Campus Drie Eiken T5.95 Universiteitsplein 1, Antwerp, 2610, Belgium
- Antwerp (Belgium) and Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
| | - Jessy Elst
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Campus Drie Eiken T5.95 Universiteitsplein 1, Antwerp, 2610, Belgium
- Antwerp (Belgium) and Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
| | - Michiel Beyens
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Campus Drie Eiken T5.95 Universiteitsplein 1, Antwerp, 2610, Belgium
- Antwerp (Belgium) and Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
| | - Margo M Hagendorens
- Department of Paediatrics and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Department of and Paediatrics, Antwerp University Hospital, Antwerp, Belgium
| | - Michel Van Houdt
- Department of Immunology, Allergology, Rheumatology and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp University Hospital, Campus Drie Eiken T5.95 Universiteitsplein 1, Antwerp, 2610, Belgium
- Antwerp (Belgium) and Immunology, Allergology, Rheumatology, Antwerp University Hospital, Antwerp, Belgium
| | - Athina L Van Gasse
- Department of Paediatrics and the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Department of and Paediatrics, Antwerp University Hospital, Antwerp, Belgium
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Sokolov P, Evsegneeva I, Karaulov A, Sukhanova A, Nabiev I. Allergen Microarrays and New Physical Approaches to More Sensitive and Specific Detection of Allergen-Specific Antibodies. BIOSENSORS 2024; 14:353. [PMID: 39056629 PMCID: PMC11275078 DOI: 10.3390/bios14070353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/16/2024] [Accepted: 07/18/2024] [Indexed: 07/28/2024]
Abstract
The prevalence of allergic diseases has increased tremendously in recent decades, which can be attributed to growing exposure to environmental triggers, changes in dietary habits, comorbidity, and the increased use of medications. In this context, the multiplexed diagnosis of sensitization to various allergens and the monitoring of the effectiveness of treatments for allergic diseases become particularly urgent issues. The detection of allergen-specific antibodies, in particular, sIgE and sIgG, is a modern alternative to skin tests due to the safety and efficiency of this method. The use of allergen microarrays to detect tens to hundreds of allergen-specific antibodies in less than 0.1 mL of blood serum enables the transition to a deeply personalized approach in the diagnosis of these diseases while reducing the invasiveness and increasing the informativeness of analysis. This review discusses the technological approaches underlying the development of allergen microarrays and other protein microarrays, including the methods of selection of the microarray substrates and matrices for protein molecule immobilization, the obtainment of allergens, and the use of different types of optical labels for increasing the sensitivity and specificity of the detection of allergen-specific antibodies.
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Affiliation(s)
- Pavel Sokolov
- Life Improvement by Future Technologies (LIFT) Center, 143025 Moscow, Russia
- Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409 Moscow, Russia
| | - Irina Evsegneeva
- Department of Clinical Immunology and Allergology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow, Russia; (I.E.); (A.K.)
| | - Alexander Karaulov
- Department of Clinical Immunology and Allergology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow, Russia; (I.E.); (A.K.)
| | - Alyona Sukhanova
- Laboratoire BioSpecT, Université de Reims Champagne-Ardenne, 51100 Reims, France;
| | - Igor Nabiev
- Life Improvement by Future Technologies (LIFT) Center, 143025 Moscow, Russia
- Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409 Moscow, Russia
- Department of Clinical Immunology and Allergology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow, Russia; (I.E.); (A.K.)
- Laboratoire BioSpecT, Université de Reims Champagne-Ardenne, 51100 Reims, France;
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Potapova E, Tripodi S, Panetta V, Dramburg S, Bernardini R, Caffarelli C, Casani A, Cervone R, Chini L, Comberiati P, De Castro G, Del Giudice MM, Dello Iacono I, Di Rienzo Businco A, Gallucci M, Giannetti A, Moschese V, Sfika I, Varin E, Asero R, Bianchi A, Calvani M, Frediani T, Macrì F, Maiello N, Paravati F, Pelosi U, Peroni D, Pingitore G, Tosca M, Zicari AM, Ricci G, Reese G, Grabenhenrich L, Icke K, Grübl A, Müller C, Zepp F, Schuster A, Wahn U, Lau S, Keil T, Matricardi PM. IgE to cross-reactive carbohydrate determinants (CCD) in childhood: Prevalence, risk factors, putative origins. Clin Exp Allergy 2024; 54:195-206. [PMID: 38234127 DOI: 10.1111/cea.14439] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 11/08/2023] [Accepted: 11/28/2023] [Indexed: 01/19/2024]
Abstract
BACKGROUND IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.
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Affiliation(s)
- Ekaterina Potapova
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Salvatore Tripodi
- Pediatric Department and Pediatric Allergology Unit, Sandro Pertini Hospital, Rome, Italy
| | | | - Stephanie Dramburg
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | | | - Carlo Caffarelli
- Department of Medicine and Surgery, Clinica Pediatrica, University of Parma, Parma, Italy
| | | | - Rosa Cervone
- Pediatric Unit, San Giuseppe Hospital, Empoli, Italy
| | - Loredana Chini
- UOSD di Immunopatologia ed Allergologia Pediatrica, Policlinico Tor Vergata, Università di Roma Tor Vergata, Rome, Italy
| | - Pasquale Comberiati
- Department of Clinical and Experimental Medicine, Section of Paediatrics, University of Pisa, Pisa, Italy
| | | | - Michele Miraglia Del Giudice
- Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Università della Campania Luigi Vanvitelli, Naples, Italy
| | | | | | - Marcella Gallucci
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Arianna Giannetti
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Viviana Moschese
- UOSD di Immunopatologia ed Allergologia Pediatrica, Policlinico Tor Vergata, Università di Roma Tor Vergata, Rome, Italy
| | - Ifigenia Sfika
- Pediatric Department and Pediatric Allergology Unit, Sandro Pertini Hospital, Rome, Italy
| | - Elena Varin
- Pediatric Intermediate Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Riccardo Asero
- Allergology Service, San Carlo Clinic, Milan, Paderno Dugnano, Italy
| | | | - Mauro Calvani
- Pediatric Unit, San Camillo Forlanini Hospital, Rome, Italy
| | | | | | - Nunzia Maiello
- Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Università della Campania Luigi Vanvitelli, Naples, Italy
| | | | | | - Diego Peroni
- Department of Life and Reproduction Sciences, Pediatric Section, University of Verona, Verona, Italy
| | | | - Mariangela Tosca
- Pulmonary Disease and Allergy Unit, G. Gaslini Hospital, Genoa, Italy
| | | | - Giampaolo Ricci
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gerald Reese
- Research and Development Division, Allergopharma Joachim Ganzer KG, Reinbek, Germany
| | - Linus Grabenhenrich
- Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Katja Icke
- Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Armin Grübl
- Department of Pediatrics, Technical University of Munich, Munich, Germany
| | - Christoph Müller
- Center for Pediatrics and Adolescent Medicine, University Medical Centre and Faculty of Medicine Freiburg, Freiburg im Breisgau, Germany
| | - Fred Zepp
- Department of Pediatrics and Adolescent Medicine, University Medicine Mainz, Mainz, Germany
| | - Antje Schuster
- Department of Pediatrics, Heinrich-Heine-University, Düsseldorf, Germany
| | - Ulrich Wahn
- Department of Pediatric Respiratory Medicine and Immunology, Former director of Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Susanne Lau
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Thomas Keil
- Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany
- State Institute of Health, Bavarian Health and Food Safety Authority, Erlangen, Germany
| | - Paolo Maria Matricardi
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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8
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Hale RC, Morais D, Chou J, Stowell SR. The role of glycosylation in clinical allergy and immunology. J Allergy Clin Immunol 2024; 153:55-66. [PMID: 37717626 PMCID: PMC10872775 DOI: 10.1016/j.jaci.2023.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 09/04/2023] [Accepted: 09/07/2023] [Indexed: 09/19/2023]
Abstract
While glycans are among the most abundant macromolecules on the cell with widespread functions, their role in immunity has historically been challenging to study. This is in part due to difficulties assimilating glycan analysis into routine approaches used to interrogate immune cell function. Despite this, recent developments have illuminated fundamental roles for glycans in host immunity. The growing field of glycoimmunology continues to leverage new tools and approaches to uncover the function of glycans and glycan-binding proteins in immunity. Here we utilize clinical vignettes to examine key roles of glycosylation in allergy, inborn errors of immunity, and autoimmunity. We will discuss the diverse functions of glycans as epitopes, as modulators of antibody function, and as regulators of immune cell function. Finally, we will highlight immune modulatory therapies that harness the critical role of glycans in the immune system.
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Affiliation(s)
- Rebecca C Hale
- Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass; Department of Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
| | - Dominique Morais
- Department of Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
| | - Janet Chou
- Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
| | - Sean R Stowell
- Department of Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Harvard Glycomics Center, Harvard Medical School, Boston, Mass.
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9
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Santos AF, Riggioni C, Agache I, Akdis CA, Akdis M, Alvarez-Perea A, Alvaro-Lozano M, Ballmer-Weber B, Barni S, Beyer K, Bindslev-Jensen C, Brough HA, Buyuktiryaki B, Chu D, Del Giacco S, Dunn-Galvin A, Eberlein B, Ebisawa M, Eigenmann P, Eiwegger T, Feeney M, Fernandez-Rivas M, Fisher HR, Fleischer DM, Giovannini M, Gray C, Hoffmann-Sommergruber K, Halken S, Hourihane JO, Jones CJ, Jutel M, Knol E, Konstantinou GN, Lack G, Lau S, Marques Mejias A, Marchisotto MJ, Meyer R, Mortz CG, Moya B, Muraro A, Nilsson C, Lopes de Oliveira LC, O'Mahony L, Papadopoulos NG, Perrett K, Peters RL, Podesta M, Poulsen LK, Roberts G, Sampson HA, Schwarze J, Smith P, Tham EH, Untersmayr E, Van Ree R, Venter C, Vickery BP, Vlieg-Boerstra B, Werfel T, Worm M, Du Toit G, Skypala I. EAACI guidelines on the diagnosis of IgE-mediated food allergy. Allergy 2023; 78:3057-3076. [PMID: 37815205 DOI: 10.1111/all.15902] [Citation(s) in RCA: 91] [Impact Index Per Article: 45.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 09/12/2023] [Accepted: 09/15/2023] [Indexed: 10/11/2023]
Abstract
This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.
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Affiliation(s)
- Alexandra F Santos
- Department of Women and Children's Health (Pediatric Allergy), Faculty of Life Sciences and Medicine, School of Life Course Sciences, King's College London, London, UK
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK
- Children's Allergy Service, Evelina London Children's Hospital, Guy's and St Thomas' Hospital, London, UK
| | - Carmen Riggioni
- Department of Allergy and Clinical Immunology, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ioana Agache
- Faculty of Medicine, Transylvania University, Brasov, Romania
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Davos, Switzerland
| | - Mubeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Davos, Switzerland
| | - Alberto Alvarez-Perea
- Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Gregorio Marañón Health Research Institute, Madrid, Spain
| | - Montserrat Alvaro-Lozano
- Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, Spain
- Institut de Recerca Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
| | - Barbara Ballmer-Weber
- Clinic for Dermatology and Allergology, Kantonsspital St. Gallen, St. Gallen, Switzerland
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Simona Barni
- Allergy Unit, Meyer Children's Hospital IRCCS, Florence, Italy
| | - Kirsten Beyer
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Carsten Bindslev-Jensen
- Department of Dermatology and Allergy Centre, Odense Research Centre for Anaphylaxis (ORCA), Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - Helen A Brough
- Department of Women and Children's Health (Pediatric Allergy), Faculty of Life Sciences and Medicine, School of Life Course Sciences, King's College London, London, UK
- Children's Allergy Service, Evelina London Children's Hospital, Guy's and St Thomas' Hospital, London, UK
| | - Betul Buyuktiryaki
- Division of Pediatric Allergy, Department of Pediatrics, Koc University School of Medicine, Istanbul, Turkey
| | - Derek Chu
- McMaster University, Ontario, Hamilton, Canada
| | - Stefano Del Giacco
- Department of Medical Sciences and Public Health and Unit of Allergy and Clinical Immunology, University Hospital "Duilio Casula", University of Cagliari, Cagliari, Italy
| | - Audrey Dunn-Galvin
- Paediatrics and Child Health, INFANT Centre, HRB-CRF, University College Cork, Cork, Ireland
- Paediatrics and Child Health, Royal College of Surgeons in Ireland, Children's Health Ireland, Dublin, Ireland
| | - Bernadette Eberlein
- Department of Dermatology and Allergy Biederstein, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Motohiro Ebisawa
- Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan
| | - Philippe Eigenmann
- Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Geneva, Switzerland
| | - Thomas Eiwegger
- Translational Medicine Program, Research Institute, Hospital for Sick Children, Ontario, Toronto, Canada
- Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Ontario, Toronto, Canada
- Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria
- Department of Pediatric and Adolescent Medicine, University Hospital St. Pölten, St.Pölten, Austria
| | - Mary Feeney
- Department of Women and Children's Health (Pediatric Allergy), Faculty of Life Sciences and Medicine, School of Life Course Sciences, King's College London, London, UK
| | - Montserrat Fernandez-Rivas
- Allergy Department, Hospital Clinico San Carlos, Madrid, Spain
- Facultad de Medicina, IdISSC, ARADyAL, Universidad Complutense, Madrid, Spain
| | - Helen R Fisher
- Department of Women and Children's Health (Pediatric Allergy), Faculty of Life Sciences and Medicine, School of Life Course Sciences, King's College London, London, UK
| | - David M Fleischer
- Children's Hospital Colorado, University of Colorado School of Medicine, Colorado, Aurora, USA
| | - Mattia Giovannini
- Allergy Unit, Meyer Children's Hospital IRCCS, Florence, Italy
- Department of Health Sciences, University of Florence, Florence, Italy
| | - Claudia Gray
- Red Cross Children's Hospital and Kidsallergy Centre, Cape Town, South Africa
- Department of Paediatrics, University of Cape Town, Cape Town, South Africa
| | - Karin Hoffmann-Sommergruber
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Susanne Halken
- Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark
| | | | - Christina J Jones
- Faculty of Medical Sciences, School of Psychology, University of Surrey, Surrey, UK
| | - Marek Jutel
- Department of Clinical Immunology, Wrocław Medical University, ALL-MED Medical Research Institute, Wroclaw, Poland
| | - Edward Knol
- Department of Dermatology/Allergology, Center of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - George N Konstantinou
- Department of Allergy and Clinical Immunology, 424 General Military Training Hospital, Thessaloniki, Greece
| | - Gideon Lack
- Department of Women and Children's Health (Pediatric Allergy), Faculty of Life Sciences and Medicine, School of Life Course Sciences, King's College London, London, UK
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK
- Children's Allergy Service, Evelina London Children's Hospital, Guy's and St Thomas' Hospital, London, UK
| | - Susanne Lau
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Andreina Marques Mejias
- Department of Women and Children's Health (Pediatric Allergy), Faculty of Life Sciences and Medicine, School of Life Course Sciences, King's College London, London, UK
- Children's Allergy Service, Evelina London Children's Hospital, Guy's and St Thomas' Hospital, London, UK
| | | | - Rosan Meyer
- Department of Medicine, Imperial College, London, UK
- Department of Nutrition and Dietetics, Winchester University, Winchester, UK
- Department of Medicine, KU Leuven, Leuven, Belgium
| | - Charlotte G Mortz
- Department of Dermatology and Allergy Centre, Odense Research Centre for Anaphylaxis (ORCA), Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - Beatriz Moya
- Department of Allergy, Hospital Universitario 12 de Octubre, Madrid, Spain
- Instituto de Investigación Sanitaria, Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Antonella Muraro
- Food Allergy Referral Centre, Padua University Hospital, Padua, Italy
| | - Caroline Nilsson
- Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden
- Sachs Children and Youth Hospital, South Hospital, Stockholm, Sweden
| | | | - Liam O'Mahony
- Department of Medicine, School of Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Nikolaos G Papadopoulos
- Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece
- Lydia Becker Institute, University of Manchester, Manchester, UK
| | - Kirsten Perrett
- Department of Paediatrics, University of Melbourne, Victoria, Parkville, Australia
- Department of Allergy and Immunology, Royal Children's Hospital, Victoria, Parkville, Australia
- Population Allergy Research Group, Murdoch Children's Research Institute, Victoria, Parkville, Australia
| | - Rachel L Peters
- Department of Paediatrics, University of Melbourne, Victoria, Parkville, Australia
- Department of Allergy and Immunology, Royal Children's Hospital, Victoria, Parkville, Australia
- Population Allergy Research Group, Murdoch Children's Research Institute, Victoria, Parkville, Australia
| | - Marcia Podesta
- EFA - European Federation of Allergy and Airways Diseases Patients' Associations, Brussels, Belgium
| | - Lars K Poulsen
- Allergy Clinic, Copenhagen University Hospital at Herlev-Gentofte, Copenhagen, Denmark
| | - Graham Roberts
- Department of Paediatric Allergy and Respiratory Medicine, University of Southampton, Southampton, UK
- NIHR Southampton Biomedical Research Centre, Southampton, UK
- David Hide Asthma and Allergy Centre, St Mary Hospital, Isle of Wight, UK
| | - Hugh A Sampson
- Division of Allergy and Immunology, Department of Pediatrics, Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
| | - Jürgen Schwarze
- Child Life and Health, Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK
| | - Peter Smith
- Clinical Medicine, Griffith University, Queensland, Southport, Australia
- Queensland Allergy Services Private Practice, Queensland, Southport, Australia
| | - Elizabeth Huiwen Tham
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Khoo Teck Puat-National University Children's Medical Institute, National University Health System (NUHS), Singapore, Singapore
- Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Eva Untersmayr
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Ronald Van Ree
- Departments of Experimental Immunology and of Otorhinolaryngoloy, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Carina Venter
- Section of Allergy and Clinical Immunology, Children's Hospital Colorado, University of Colorado, Colorado, Aurora, USA
| | - Brian P Vickery
- Emory University School of Medicine and Children's Healthcare of Atlanta, Georgia, Atlanta, USA
| | - Berber Vlieg-Boerstra
- Department of Paediatrics, OLVG Hospital, Amsterdam, the Netherlands
- Rijnstate Allergy Centre, Rijnstate Hospital, Arnhem, The Netherlands
- Vlieg Dieticians, Private Practice for Dietary Management of Food Allergy, Arnhem, The Netherlands
| | - Thomas Werfel
- Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany
| | - Margitta Worm
- Division of Allergy and immunology, Department of Dermatology, Venerology and Allergology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - George Du Toit
- Department of Women and Children's Health (Pediatric Allergy), Faculty of Life Sciences and Medicine, School of Life Course Sciences, King's College London, London, UK
- Children's Allergy Service, Evelina London Children's Hospital, Guy's and St Thomas' Hospital, London, UK
| | - Isabel Skypala
- Royal Brompton & Harefield Hospitals, Part of Guys & St Thomas NHS Foundation Trust, London, UK
- Department of Inflammation and Repair, Imperial College, London, UK
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10
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Kasper B, Boehm T, Wittenstein N, Mueller RS. Cross-reactive carbohydrate determinants in atopic and healthy dogs and their influence on allergy test specificity. Vet Rec 2023; 193:e3308. [PMID: 37614212 DOI: 10.1002/vetr.3308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 07/01/2023] [Accepted: 07/07/2023] [Indexed: 08/25/2023]
Abstract
BACKGROUND The selection of allergens for immunotherapy in atopic dogs is often based on serum allergy testing. Cross-reactive carbohydrate determinants (CCDs) are common structures in plant and insect allergens that reportedly induce polysensitisation, reduce agreement between intradermal and serum tests and complicate allergen selection. METHODS Thirty-four dogs with diagnosed atopic dermatitis and 10 healthy dogs were included in the study. An intradermal test was conducted in atopic dogs, and serum samples from allergic and healthy dogs were analysed for allergen-specific immunoglobulin E (IgE) before and after inhibition of detectable anti-CCD-IgE antibodies. RESULTS Anti-CCD-IgE antibodies were not found in any of the healthy dogs and no polysensitisation to plant and insect allergens was detected. The agreement between intradermal and serum allergy test results in the atopic dogs with anti-CCD-IgE antibodies improved from slight to fair after blocking the anti-CCD-IgE antibodies. In addition, blocking clearly reduced polysensitisation to plant allergens but not to acarid allergens. LIMITATIONS Only a limited number of healthy dogs were tested in this study. A gold standard for determining the clinical relevance of IgE sensitisation does not exist. CONCLUSION Inhibition of anti-CCD-IgE antibodies seems to be of importance to improve serum test specificity for allergen-specific IgE in atopic dogs in relation to intradermal allergy testing.
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Affiliation(s)
- Bettina Kasper
- Center of Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Teresa Boehm
- Center of Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | | | - Ralf S Mueller
- Center of Clinical Veterinary Medicine, LMU Munich, Munich, Germany
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11
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Hörner-Schmid L, Palić J, Mueller RS, Schulz B. Serum Allergen-Specific Immunoglobulin E in Cats with Inflammatory Bronchial Disease. Animals (Basel) 2023; 13:3226. [PMID: 37893950 PMCID: PMC10603667 DOI: 10.3390/ani13203226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/13/2023] [Accepted: 10/14/2023] [Indexed: 10/29/2023] Open
Abstract
The etiology of feline inflammatory bronchial disease is poorly understood. This study compares the degree of allergen-specific serum IgE responses between cats with feline asthma, chronic bronchitis, mixed inflammation, and clinically healthy cats (HCs). The retrospective case-control study used serum from eighteen cats with eosinophilic inflammation (EI), ten with neutrophilic inflammation (NI), six with mixed inflammation (MI), and fourteen HCs. Affected cats were categorized into groups based on bronchoalveolar lavage cytology. The measurement of IgE for 34 different allergens including fungal organisms, weeds, grasses, trees, mites, and insects was performed using an indirect ELISA. Positive reactions to allergens were detected in the serum of 17/18 cats with EI, 8/10 with NI, 6/6 with MI, and 11/14 HCs (p = 0.364). When overall positive reactions were compared between groups, cats with MI (p = <0.01) had significantly more positive reactions against mite allergens than HCs. Blood eosinophils inversely correlated with the absolute amount of allergen-specific serum IgE expressed in ELISA absorbance units (EAs) (p = 0.014). Sensitization against dust mites seems to be more prevalent in cats with MI. However, positive IgE reactions can be observed in healthy and diseased cats, and, therefore, need to be interpreted in the light of clinical findings and environmental conditions of individual patients.
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Affiliation(s)
| | - Jelena Palić
- Vet Med Labor GmbH Division of IDEXX Laboratories, 70806 Kornwestheim, Germany
| | - Ralf S. Mueller
- LMU Small Animal Clinic, University of Munich, 80539 Munich, Germany
| | - Bianka Schulz
- LMU Small Animal Clinic, University of Munich, 80539 Munich, Germany
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12
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Lis K, Bartuzi Z. Selected Technical Aspects of Molecular Allergy Diagnostics. Curr Issues Mol Biol 2023; 45:5481-5493. [PMID: 37504263 PMCID: PMC10378047 DOI: 10.3390/cimb45070347] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 06/21/2023] [Accepted: 06/28/2023] [Indexed: 07/29/2023] Open
Abstract
Diagnosis of allergic diseases is a complex, multi-stage process. It often requires the use of various diagnostic tools. The in vitro diagnostics (IVD), which includes various laboratory tests, is one of the stages of this process. Standard laboratory tests include the measurement of the serum concentration of specific immunoglobulin E (sIgE) for selected allergens, full allergen extracts and/or single allergen components (molecules). The measurement of IgE sIgE to the allergen components is called molecular allergy diagnosis. During the standard laboratory diagnostic process, various models of immunochemical tests are used, which enable the measurement of sIgE for single allergens (one-parameter tests, singleplex) or IgE specific for many different allergens (multi-parameter tests, multiplex) in one test. Currently, there are many different test kits available, validated for IVD, which differ in the method type and allergen profile. The aim of the manuscript is to present various technical aspects related to modern allergy diagnostics, especially in the area of molecular allergy diagnostics.
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Affiliation(s)
- Kinga Lis
- Department of Allergology, Clinical Immunology and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-168 Bydgoszcz, Poland
| | - Zbigniew Bartuzi
- Department of Allergology, Clinical Immunology and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-168 Bydgoszcz, Poland
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13
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Rainyte J, Zvirblis G, Zaveckas M, Kucinskaite-Kodze I, Silimavicius L, Petraityte-Burneikiene R. Immunological comparison of recombinant shrimp allergen Pen m 4, produced in Pichia pastoris and Escherichia coli. J Biotechnol 2023; 369:1-13. [PMID: 37164269 DOI: 10.1016/j.jbiotec.2023.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 04/24/2023] [Accepted: 05/05/2023] [Indexed: 05/12/2023]
Abstract
Shellfish are a leading cause of allergies worldwide, affecting about one-tenth of the general population. The sarcoplasmic calcium-binding protein, also known as allergen Pen m 4, is an important factor in shrimp allergies. Our objective was to assess the most effective techniques for producing a recombinant Pen m 4 protein as a potential tool for diagnosing shrimp allergies. In this study, for the first time, we produced a functional recombinant Pen m 4 protein in a eukaryotic system, Pichia pastoris, and analyzed it against Escherichia coli-produced equivalents in enzyme-linked immunosorbent and reverse-phase protein microarray assays. A dual tag system based on the maltose-binding protein was successfully used to increase the yield of Pen m 4 by 1.3 to 2.3-fold in both bacteria and yeast, respectively. Immunological characterization showed that N-glycosylation is neither crucial for the folding of Pen m 4 nor its recognition by specific IgE. However, the Ca2+-depletion assay indicated a dependence on calcium ion presence in blood samples. Results demonstrate how a comparative analysis can elucidate essential allergen manufacturing points. In conclusion, E. coli-produced Pen m 4 protein fused with the maltose-binding protein should be the preferred option for further studies in Penaeus monodon allergy diagnostics.
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Affiliation(s)
- Juta Rainyte
- Vilnius University Life Sciences Center Institute of Biotechnology, Sauletekio av. 7, 10257 Vilnius, Lithuania.
| | - Gintautas Zvirblis
- Vilnius University Life Sciences Center Institute of Biotechnology, Sauletekio av. 7, 10257 Vilnius, Lithuania.
| | - Mindaugas Zaveckas
- Vilnius University Life Sciences Center Institute of Biotechnology, Sauletekio av. 7, 10257 Vilnius, Lithuania.
| | - Indre Kucinskaite-Kodze
- Vilnius University Life Sciences Center Institute of Biotechnology, Sauletekio av. 7, 10257 Vilnius, Lithuania.
| | - Laimis Silimavicius
- Vilnius University Life Sciences Center Institute of Biotechnology, Sauletekio av. 7, 10257 Vilnius, Lithuania; Imunodiagnostika Ltd., Moletu str. 16, 14260 Vilnius, Lithuania.
| | - Rasa Petraityte-Burneikiene
- Vilnius University Life Sciences Center Institute of Biotechnology, Sauletekio av. 7, 10257 Vilnius, Lithuania.
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14
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Prasanphanich NS, Leon K, Secor WE, Shoemaker CB, Heimburg-Molinaro J, Cummings RD. Anti-schistosomal immunity to core xylose/fucose in N-glycans. Front Mol Biosci 2023; 10:1142620. [PMID: 37081851 PMCID: PMC10110957 DOI: 10.3389/fmolb.2023.1142620] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 03/20/2023] [Indexed: 04/07/2023] Open
Abstract
Schistosomiasis is a globally prevalent, debilitating disease that is poorly controlled by chemotherapy and for which no vaccine exists. While partial resistance in people may develop over time with repeated infections and treatments, some animals, including the brown rat (Rattus norvegicus), are only semi-permissive and have natural protection. To understand the basis of this protection, we explored the nature of the immune response in the brown rat to infection by Schistosoma mansoni. Infection leads to production of IgG to Infection leads to production of IgG to parasite glycoproteins parasite glycoproteins with complex-type N-glycans that contain a non-mammalian-type modification by core α2-Xylose and core α3-Fucose (core Xyl/Fuc). These epitopes are expressed on the surfaces of schistosomula and adult worms. Importantly, IgG to these epitopes can kill schistosomula by a complement-dependent process in vitro. Additionally, sera from both infected rhesus monkey and infected brown rat were capable of killing schistosomula in a manner inhibited by glycopeptides containing core Xyl/Fuc. These results demonstrate that protective antibodies to schistosome infections in brown rats and rhesus monkeys include IgG responses to the core Xyl/Fuc epitopes in surface-expressed N-glycans, and raise the potential of novel glyco-based vaccines that might be developed to combat this disease.
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Affiliation(s)
| | - Kristoffer Leon
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, United States
| | - W. Evan Secor
- Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Charles B. Shoemaker
- Department of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, United States
| | - Jamie Heimburg-Molinaro
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, United States
- National Center for Functional Glycomics, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Richard D. Cummings
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, United States
- National Center for Functional Glycomics, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- *Correspondence: Richard D. Cummings,
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Lecolant S, Khelifi D, Neukirch C, Taillé C, Chabane H, Giboury Lafarge S, Sève E, Pham Thi N, Epstein M, Chollet Martin S, Nicaise Roland P. Comparaison des performances diagnostiques de deux biopuces IgE : ISAC® et ALEX2®. REVUE FRANÇAISE D'ALLERGOLOGIE 2023. [DOI: 10.1016/j.reval.2023.103289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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C-Type Lectin Receptor Mediated Modulation of T2 Immune Responses to Allergens. Curr Allergy Asthma Rep 2023; 23:141-151. [PMID: 36720753 PMCID: PMC9985561 DOI: 10.1007/s11882-023-01067-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/12/2022] [Indexed: 02/02/2023]
Abstract
PURPOSE OF REVIEW Allergic diseases represent a major health problem of increasing prevalence worldwide. In allergy, dendritic cells (DCs) contribute to both the pathophysiology and the induction of healthy immune responses to the allergens. Different studies have reported that some common allergens contain glycans in their structure. C-type lectin receptors (CLRs) expressed by DCs recognize carbohydrate structures and are crucial in allergen uptake, presentation, and polarization of T cell responses. This review summarizes the recent literature regarding the role of CLRs in the regulation of type 2 immune responses to allergens. RECENT FINDINGS In this review, we highlight the capacity of CLRs to recognize carbohydrates in common allergens triggering different signaling pathways involved in the polarization of CD4+ T cells towards specific Th2 responses. Under certain conditions, specific CLRs could also promote tolerogenic responses to allergens, which might well be exploited to develop novel therapeutic approaches of allergen-specific immunotherapy (AIT), the single treatment with potential disease-modifying capacity for allergic disease. At this regard, polymerized allergens conjugated to non-oxidized mannan (allergoid-mannan conjugated) are next-generation vaccines targeting DCs via CLRs that promote regulatory T cells, thus favoring allergen tolerance both in preclinical models and clinical trials. A better understanding of the role of CLRs in the development of allergy and in the induction of allergen tolerance might well pave the way for the design of novel strategies for allergic diseases.
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Foo ACY, Nesbit JB, Gipson SAY, DeRose EF, Cheng H, Hurlburt BK, Kulis MD, Kim EH, Dreskin SC, Mustafa S, Maleki SJ, Mueller GA. Structure and IgE Cross-Reactivity among Cashew, Pistachio, Walnut, and Peanut Vicilin-Buried Peptides. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:2990-2998. [PMID: 36728846 PMCID: PMC10402694 DOI: 10.1021/acs.jafc.2c07061] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Peanut and tree-nut allergies are frequently comorbid for reasons not completely understood. Vicilin-buried peptides (VBPs) are an emerging family of food allergens whose conserved structural fold could mediate peanut/tree-nut co-allergy. Peptide microarrays were used to identify immunoglobulin E (IgE) epitopes from the N-terminus of the vicilin allergens Ara h 1, Ana o 1, Jug r 2, and Pis v 3 using serum from three patient diagnosis groups: monoallergic to either peanuts or cashew/pistachio, or dual allergic. IgE binding peptides were highly prevalent in the VBP domains AH1.1, AO1.1, JR2.1, and PV3.1, but not in AO1.2, JR2.2, JR2.3, and PV3.2 nor the unstructured regions. The IgE profiles did not correlate with diagnosis group. The structure of the VBPs from cashew and pistachio was solved using solution-NMR. Comparisons of structural features suggest that the VBP scaffold from peanuts and tree-nuts can support cross-reactivity. This may help understand comorbidity and cross-reactivity despite a distant evolutionary origin.
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Affiliation(s)
- Alexander C Y Foo
- Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, MD-MR01, Durham, North Carolina 27709, United States
| | - Jacqueline B Nesbit
- Agricultural Research Service, United States Department of Agriculture, 1100 Allen Toussaint Boulevard, New Orleans, Louisiana 70124, United States
| | - Stephen A Y Gipson
- Agricultural Research Service, United States Department of Agriculture, 1100 Allen Toussaint Boulevard, New Orleans, Louisiana 70124, United States
| | - Eugene F DeRose
- Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, MD-MR01, Durham, North Carolina 27709, United States
| | - Hsiaopo Cheng
- Agricultural Research Service, United States Department of Agriculture, 1100 Allen Toussaint Boulevard, New Orleans, Louisiana 70124, United States
| | - Barry K Hurlburt
- Agricultural Research Service, United States Department of Agriculture, 1100 Allen Toussaint Boulevard, New Orleans, Louisiana 70124, United States
| | - Michael D Kulis
- Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7220, United States
| | - Edwin H Kim
- Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7220, United States
| | - Stephen C Dreskin
- Division of Allergy and Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado 80045-2560, United States
| | - Shahzad Mustafa
- Rochester Regional Health, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, United States
| | - Soheila J Maleki
- Agricultural Research Service, United States Department of Agriculture, 1100 Allen Toussaint Boulevard, New Orleans, Louisiana 70124, United States
| | - Geoffrey A Mueller
- Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, MD-MR01, Durham, North Carolina 27709, United States
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Lis K, Ukleja-Sokołowska N, Karwowska K, Wernik J, Pawłowska M, Bartuzi Z. The Two-Sided Experimental Model of ImmunoCAP Inhibition Test as a Useful Tool for the Examination of Allergens Cross-Reactivity on the Example of α-Gal and Mammalian Meat Sensitization-A Preliminary Study. Curr Issues Mol Biol 2023; 45:1168-1182. [PMID: 36826022 PMCID: PMC9955645 DOI: 10.3390/cimb45020077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/25/2023] [Accepted: 01/30/2023] [Indexed: 02/04/2023] Open
Abstract
Cross-reactivity of allergens is the cause of various, sometimes unexpected, clinical reactions. There are no standard methods to investigate cross-reactivity. We present an experimental model of a two-sided inhibition test (IT) on ImmunoCAP membranes (CAP). We constructed the described model based on the known cross-allergy syndrome to red meat developing in people bitten by ticks (α-Gal syndrome; AGS). Some individuals who are bitten by ticks develop IgE antibodies specific to the carbohydrate determinant, galactose-α-1,3-galactose (α-Gal), present in the tick's saliva. These antibodies can cross-react with α-Gal molecules expressed on mammalian meat proteins. The well-known property of anti-α-Gal IgE antibodies binding by various sources of this allergen was used by us in the proposed model of the two-sided inhibition test on ImmunoCAP membranes. We expected that anti-α-Gal IgE antibodies bind allergens from mammalian meat and blocking them abolishes this reactivity, and the two-sided inhibition test model we proposed on ImmunoCAP membranes allowed us to observe such a relationship. We conducted the experiment three times on biological material from people with different clinical manifestations of allergy to α-Gal, each time obtaining similar results. In conclusion, the model of bilateral inhibition on ImmunoCAP membranes proposed by us seems to be an attractive, simple tool for direct testing of allergic cross-reactivity.
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Affiliation(s)
- Kinga Lis
- Department of Allergology, Clinical Immunology and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Ujejskiego 75, 85168 Bydgoszcz, Poland
- Correspondence:
| | - Natalia Ukleja-Sokołowska
- Department of Allergology, Clinical Immunology and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Ujejskiego 75, 85168 Bydgoszcz, Poland
| | - Kornelia Karwowska
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Świętego Floriana 12, 85030 Bydgoszcz, Poland
| | - Joanna Wernik
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Świętego Floriana 12, 85030 Bydgoszcz, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Świętego Floriana 12, 85030 Bydgoszcz, Poland
| | - Zbigniew Bartuzi
- Department of Allergology, Clinical Immunology and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Ujejskiego 75, 85168 Bydgoszcz, Poland
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Component-Resolved Diagnosis Based on a Recombinant Variant of Mus m 1 Lipocalin Allergen. Int J Mol Sci 2023; 24:ijms24021193. [PMID: 36674705 PMCID: PMC9862564 DOI: 10.3390/ijms24021193] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/21/2022] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
Exposure to the Mus m 1 aeroallergen is a significant risk factor for laboratory animal allergy. This allergen, primarily expressed in mouse urine where it is characterized by a marked and dynamic polymorphism, is also present in epithelium and dander. Considering the relevance of sequence/structure assessment in protein antigenic reactivity, we compared the sequence of the variant Mus m 1.0102 to other members of the Mus m 1 allergen, and used Discotope 2.0 to predict conformational epitopes based on its 3D-structure. Conventional diagnosis of mouse allergy is based on serum IgE testing, using an epithelial extract as the antigen source. Given the heterogeneous and variable composition of extracts, we developed an indirect ELISA assay based on the recombinant component Mus m 1.0102. The assay performed with adequate precision and reasonable diagnostic accuracy (AUC = 0.87) compared to a routine clinical diagnostic test that exploits the native allergen. Recombinant Mus m 1.0102 turned out to be a valuable tool to study the fine epitope mapping of specific IgE reactivity to the major allergen responsible for mouse allergy. We believe that advancing in its functional characterization will lead to the standardization of murine lipocalins and to the development of allergen-specific immunotherapy.
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20
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Hopke K, Coleman M, Kneese E, Dominguez B, Diesel A, Patterson A. Prevalence of serum immunoglobulin E against cross‐reactive carbohydrate determinants in allergic and nonallergic horses, and its impact on polysensitisation in serum allergen tests. Vet Dermatol 2022; 33:338-e79. [DOI: 10.1111/vde.13073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 01/11/2022] [Accepted: 01/18/2022] [Indexed: 11/28/2022]
Affiliation(s)
- Kaitlin Hopke
- Department of Small Animal Clinical Sciences College of Veterinary Medicine, Texas A&M University TX USA
| | - Michelle Coleman
- Large Animal Clinical Sciences College of Veterinary Medicine, Texas A&M University TX USA
| | - Eric Kneese
- Large Animal Clinical Sciences College of Veterinary Medicine, Texas A&M University TX USA
| | - Brandon Dominguez
- Large Animal Clinical Sciences College of Veterinary Medicine, Texas A&M University TX USA
| | - Alison Diesel
- Department of Small Animal Clinical Sciences College of Veterinary Medicine, Texas A&M University TX USA
| | - Adam Patterson
- Department of Small Animal Clinical Sciences College of Veterinary Medicine, Texas A&M University TX USA
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Chen H, Jiang Q, Yang Y, Zhang W, Yang L, Zhu R. Cross-Reacting Carbohydrate Determinants Inhibitor Can Improve the Diagnostic Accuracy in Pollen and Food Allergy. J Asthma Allergy 2022; 15:713-725. [PMID: 35645572 PMCID: PMC9139414 DOI: 10.2147/jaa.s363206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 05/17/2022] [Indexed: 12/03/2022] Open
Abstract
Background Cross-reacting carbohydrate determinants (CCD) exist in some pollen and food allergens, but they do not contribute to allergic symptoms. However, CCD can induce specific IgE (sIgE) production and may lead to incorrect allergen diagnosis and treatment. CCD inhibitor is a specific antibody adsorbent which can preclude CCD from binding to sIgE. Currently, the data of CCD inhibition in allergen sIgE test are limited. Methods The allergic patients with positive skin prick reactions to two or more pollen and/or food allergen extracts were included in our study. Their sera were obtained and sIgE was tested with an allergen panel that included 29 single and mixed allergens (MEDIWISS Analytic GmbH, China) before and after CCD inhibition. The changes of sIgE against these allergens and the correlations of sIgEs to clinical symptoms were analyzed. Results A total of 44 patients were included and 36 (81.82%) of those were multi-sensitized to house dust mites and pollen allergens based on skin prick tests. The sIgE levels and positive rates against most pollen and food allergens were significantly lower after CCD inhibition. The sIgE levels of pollen were positively correlated to those of food allergens before CCD inhibition. However, these correlations were weakened or no longer existed after CCD inhibition. The sIgE against pollen and food allergens showed significantly higher consistency with clinical symptoms after CCD inhibition. Conclusion Cross-sensitization caused by CCD is widespread in pollen and food. CCD inhibition test can improve the diagnostic accuracy of pollen and food allergy.
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Affiliation(s)
- Hao Chen
- Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China
| | - Qing Jiang
- Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China
| | - Yaqi Yang
- Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China
| | - Wei Zhang
- Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China
| | - Lin Yang
- Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China
| | - Rongfei Zhu
- Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China
- Correspondence: Rongfei Zhu, Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China, Tel/Fax +86-27-8366 2912, Email
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22
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Lee LYGN, Leow SY, Wen H, Soh JY, Chiang WC, Zhong Y, Tham EH, Loh W, Delsing DJ, Lee BW, Huang CH. An Evaluation of the Mechanisms of Galacto-Oligosaccharide (GOS)-Induced IgE Cross-Linking on Basophils in GOS Allergy. FRONTIERS IN ALLERGY 2022; 3:840454. [PMID: 35386657 PMCID: PMC8974727 DOI: 10.3389/falgy.2022.840454] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 01/31/2022] [Indexed: 12/02/2022] Open
Abstract
The prebiotics, galacto-oligosaccharides (GOS), are small carbohydrate molecules with 1–7 galactose units linked to glucose and have been shown to trigger IgE-mediated anaphylaxis in some cases following ingestion. It is still an unresolved question of how GOS cross-links IgE on basophils. In this study, we examined whether human galectins, a class of lectins that bind specifically to β-galactoside carbohydrates, are involved in GOS-induced basophil activation. Basophil activation test to GOS and control allergen, Blomia tropicalis (Blo t) extract were performed in the presence or absence of four sugar-based galectin inhibitors (lactose, thiodigalactoside [TDG], TD139, and GB1107) and one peptide-based inhibitor, G3-C12. Results showed that TD139, GB1107, and G3-C12 did not display a specific inhibitory effect on GOS-induced basophil activation as compared to control allergen. An inhibitory effect of lactose and TDG on GOS-induced basophil activation was observed and varied between subjects with up to 100% inhibition at low doses of GOS. The results of competitive ELISA suggest that the inhibitory effects of high dose lactose and TDG on the basophil activation is likely due to the cross-reactivity of GOS-specific IgE to lactose and TDG. Basophil activation is performed using purified basophils suggested that cell surface receptors on other blood cells were not required to induce basophil activation. In conclusion, our results suggest that GOS, a low molecular weight sugar, is able to cross-link IgE independently.
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Affiliation(s)
- Li Yuan Gabriella Nadine Lee
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Si Yuan Leow
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Hongmei Wen
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jian Yi Soh
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore
| | - Wen Chin Chiang
- Department of Paediatrics, Kandang Kerbau Women's and Children's Hospital, Singapore, Singapore
| | - Youjia Zhong
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore
| | - Elizabeth Huiwen Tham
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore
| | - Wenyin Loh
- Department of Paediatrics, Kandang Kerbau Women's and Children's Hospital, Singapore, Singapore
| | | | - Bee Wah Lee
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chiung-Hui Huang
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- *Correspondence: Chiung-Hui Huang
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23
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Kiewiet MBG, Perusko M, Grundström J, Hamsten C, Starkhammar M, Apostolovic D, van Hage M. Cross-reactivity between tick and wasp venom can contribute to frequent wasp sensitization in patients with the α-Gal syndrome. Clin Transl Allergy 2022; 12:e12113. [PMID: 35070272 PMCID: PMC8762686 DOI: 10.1002/clt2.12113] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 01/01/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND α-Gal syndrome (AGS) is a food allergy with severe delayed allergic reactions, mediated by IgE-reactivity to galactose-α1,3-galactose (α-Gal). AGS is strongly associated with tick bites. An increased incidence of venom sensitization has been found in AGS patients. Here, we evaluated the frequency of wasp sensitization in Swedish AGS patients and the possible cross-reactivity between wasp venom and tick proteins. METHODS Sera from 136 Swedish AGS patients and 29 wasp-positive non-AGS control sera were analyzed for IgE-reactivity against wasp venom (Vespula spp.), the European tick Ixodes ricinus (Streptavidin ImmunoCAP), α-Gal and total IgE by ImmunoCAP. The presence of α-Gal on wasp venom proteins (Vespula vulgaris) was investigated by western blot (WB), and possible cross-reactivity between wasp venom and tick proteins by enzyme-linked immunosorbent assay and WB. Involvement of cross-reactive carbohydrate domains (CCDs) was also assessed. RESULTS Wasp sensitization was present in 54% of AGS patients, although the IgE levels were low. Wasp sensitized patients had higher IgE levels to α-Gal and total IgE levels compared to non-wasp sensitized AGS patients. α-Gal was not detected in wasp venom, but cross-reactivity between wasp and tick proteins was demonstrated which was not dependent on CCDs. The same cross-reactivity was also observed in the control sera. Furthermore, 17 putative cross-reactive peptides were identified using an in silico approach. CONCLUSIONS For the first time, cross-reactivity between wasp venom and tick proteins has been described. This may be a reason why the majority of Swedish AGS patients, who have all been tick bitten, are also sensitized against wasp.
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Affiliation(s)
- Mensiena B. G. Kiewiet
- Division of Immunology and AllergyDepartment of Medicine SolnaKarolinska Institutet and University HospitalStockholmSweden
| | - Marija Perusko
- Division of Immunology and AllergyDepartment of Medicine SolnaKarolinska Institutet and University HospitalStockholmSweden
| | - Jeanette Grundström
- Division of Immunology and AllergyDepartment of Medicine SolnaKarolinska Institutet and University HospitalStockholmSweden
| | - Carl Hamsten
- Division of Immunology and AllergyDepartment of Medicine SolnaKarolinska Institutet and University HospitalStockholmSweden
| | | | - Danijela Apostolovic
- Division of Immunology and AllergyDepartment of Medicine SolnaKarolinska Institutet and University HospitalStockholmSweden
| | - Marianne van Hage
- Division of Immunology and AllergyDepartment of Medicine SolnaKarolinska Institutet and University HospitalStockholmSweden
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Román-Carrasco P, Hemmer W, Cabezas-Cruz A, Hodžić A, de la Fuente J, Swoboda I. The α-Gal Syndrome and Potential Mechanisms. FRONTIERS IN ALLERGY 2021; 2:783279. [PMID: 35386980 PMCID: PMC8974695 DOI: 10.3389/falgy.2021.783279] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 11/08/2021] [Indexed: 12/17/2022] Open
Abstract
The α-Gal syndrome is a complex allergic disease characterized by the development of specific IgE antibodies against the carbohydrate galactose-α-1,3-galactose (α-Gal), an oligosaccharide present in cells and tissues of non-primate mammals. Individuals with IgE antibodies to α-Gal suffer from a delayed form of anaphylaxis following red meat consumption. There are several features that make the α-Gal syndrome such a unique allergic disease and distinguish it from other food allergies: (1) symptoms causing IgE antibodies are directed against a carbohydrate moiety, (2) the unusual delay between the consumption of the food and the onset of the symptoms, and (3) the fact that primary sensitization to α-Gal occurs via tick bites. This review takes a closer look at the immune response against α-Gal, in healthy and in α-Gal allergic individuals. Furthermore, the similarities and differences between immune response against α-Gal and against the other important glycan moieties associated with allergies, namely cross-reactive carbohydrate determinants (CCDs), are discussed. Then different mechanisms are discussed that could contribute to the delayed onset of symptoms after consumption of mammalian meat. Moreover, our current knowledge on the role of tick bites in the sensitization process is summarized. The tick saliva has been shown to contain proteins carrying α-Gal, but also bioactive molecules, such as prostaglandin E2, which is capable of stimulating an increased expression of anti-inflammatory cytokines while promoting a decrease in the production of proinflammatory mediators. Together these components might promote Th2-related immunity and trigger a class switch to IgE antibodies directed against the oligosaccharide α-Gal. The review also points to open research questions that remain to be answered and proposes future research directions, which will help to get a better understanding and lead to a better management of the disease.
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Affiliation(s)
- Patricia Román-Carrasco
- Molecular Biotechnology Section, FH Campus Wien, University of Applied Sciences, Vienna, Austria
| | | | - Alejandro Cabezas-Cruz
- Anses, INRAE, Ecole Nationale Vétérinaire d'Alfort, UMR BIPAR, Laboratoire de Santé Animale, Maisons-Alfort, France
| | - Adnan Hodžić
- Department of Pathobiology, Institute of Parasitology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - José de la Fuente
- SaBio, Instituto de Investigación de Recursos Cinegéticos, IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain
- Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States
| | - Ines Swoboda
- Molecular Biotechnology Section, FH Campus Wien, University of Applied Sciences, Vienna, Austria
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25
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Stanly C, Kim H, Antonucci G, Fiume I, Guescini M, Kim KP, Ciardiello MA, Giangrieco I, Mari A, Pocsfalvi G. Crosstalk Between the Immune System and Plant-Derived Nanovesicles: A Study of Allergen Transporting. Front Bioeng Biotechnol 2021; 9:760730. [PMID: 34900959 PMCID: PMC8662998 DOI: 10.3389/fbioe.2021.760730] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Nanometer-sized membrane-surrounded vesicles from different parts of plants including fruits are gaining increasing attention due to their anti-inflammatory and anticancer effects demonstrated by in vitro and in vivo studies, and as nanovectors for molecular delivery of exogenous substances. These nanomaterials are very complex and contain a diverse arsenal of bioactive molecules, such as nucleic acids, proteins, and lipids. Our knowledge about the transport of allergens in vesicles isolated from plant food is limited today. Methods: Here, to investigate the allergenicity of strawberry-derived microvesicles (MVs), nanovesicles (NVs), and subpopulations of NV, we have set up a multidisciplinary approach. The strategy combines proteomics-based protein identification, immunological investigations, bioinformatics, and data mining to gain biological insights useful to evaluate the presence of potential allergens and the immunoglobulin E (IgE) inhibitory activity of vesicle preparations. Results: Immunological test showed that several proteins of strawberry-derived vesicles compete for IgE binding with allergens spotted on the FABER biochip. This includes the known strawberry allergens Fra a 1, Fra a 3, and Fra a 4, and also other IgE-binding proteins not yet described as allergens in this food, such as gibberellin-regulated proteins, 2S albumin, pectate lyase, and trypsin inhibitors. Proteomics identified homologous sequences of the three strawberry allergens and their isoforms in total protein extract (TPE) but only Fra a 1 and Fra a 4 in the vesicle samples. Label-free quantitative proteomic analysis revealed no significant enrichment of these proteins in strawberry vesicles with respect to TPE. Conclusion: Immunological tests and bioinformatics analysis of proteomics data sets revealed that MVs and NVs isolated from strawberries can carry functional allergens their isoforms as well as proteins potentially allergenic based on their structural features. This should be considered when these new nanomaterials are used for human nutraceutical or biomedical applications.
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Affiliation(s)
- Christopher Stanly
- Institute of Biosciences and Bioresources, National Research Council of Italy, Naples, Italy
| | - Hyoseon Kim
- Department of Applied Chemistry, Institute of Natural Science, Kyung Hee University, Yongin, South Korea
- Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul, South Korea
| | - Giuseppe Antonucci
- Institute of Biosciences and Bioresources, National Research Council of Italy, Naples, Italy
| | - Immacolata Fiume
- Institute of Biosciences and Bioresources, National Research Council of Italy, Naples, Italy
| | - Michele Guescini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy
| | - Kwang Pyo Kim
- Department of Applied Chemistry, Institute of Natural Science, Kyung Hee University, Yongin, South Korea
- Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul, South Korea
| | | | - Ivana Giangrieco
- Institute of Biosciences and Bioresources, National Research Council of Italy, Naples, Italy
- Allergy Data Laboratories (ADL), Latina, Italy
| | - Adriano Mari
- Allergy Data Laboratories (ADL), Latina, Italy
- Associated Centers for Molecular Allergology (CAAM), Rome, Italy
| | - Gabriella Pocsfalvi
- Institute of Biosciences and Bioresources, National Research Council of Italy, Naples, Italy
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Schwestka J, König-Beihammer J, Shin YJ, Vavra U, Kienzl NF, Grünwald-Gruber C, Maresch D, Klausberger M, Laurent E, Stadler M, Manhart G, Huber J, Hofner M, Vierlinger K, Weinhäusel A, Swoboda I, Binder CJ, Gerner W, Grebien F, Altmann F, Mach L, Stöger E, Strasser R. Impact of Specific N-Glycan Modifications on the Use of Plant-Produced SARS-CoV-2 Antigens in Serological Assays. FRONTIERS IN PLANT SCIENCE 2021; 12:747500. [PMID: 34646292 PMCID: PMC8503525 DOI: 10.3389/fpls.2021.747500] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 09/08/2021] [Indexed: 05/04/2023]
Abstract
The receptor binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in the virus-host cell interaction, and viral infection. The RBD is a major target for neutralizing antibodies, whilst recombinant RBD is commonly used as an antigen in serological assays. Such assays are essential tools to gain control over the pandemic and detect the extent and durability of an immune response in infected or vaccinated populations. Transient expression in plants can contribute to the fast production of viral antigens, which are required by industry in high amounts. Whilst plant-produced RBDs are glycosylated, N-glycan modifications in plants differ from humans. This can give rise to the formation of carbohydrate epitopes that can be recognized by anti-carbohydrate antibodies present in human sera. For the performance of serological tests using plant-produced recombinant viral antigens, such cross-reactive carbohydrate determinants (CCDs) could result in false positives. Here, we transiently expressed an RBD variant in wild-type and glycoengineered Nicotiana benthamiana leaves and characterized the impact of different plant-specific N-glycans on RBD reactivity in serological assays. While the overall performance of the different RBD glycoforms was comparable to each other and to a human cell line produced RBD, there was a higher tendency toward false positive results with sera containing allergy-related CCD-antibodies when an RBD carrying β1,2-xylose and core α1,3-fucose was used. These rare events could be further minimized by pre-incubating sera from allergic individuals with a CCD-inhibitor. Thereby, false positive signals obtained from anti-CCD antibodies, could be reduced by 90%, on average.
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Affiliation(s)
- Jennifer Schwestka
- Department of Applied Genetics and Cell Biology, Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Julia König-Beihammer
- Department of Applied Genetics and Cell Biology, Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Yun-Ji Shin
- Department of Applied Genetics and Cell Biology, Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Ulrike Vavra
- Department of Applied Genetics and Cell Biology, Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Nikolaus F. Kienzl
- Department of Applied Genetics and Cell Biology, Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Clemens Grünwald-Gruber
- Department of Chemistry, Institute of Biochemistry, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Daniel Maresch
- Department of Chemistry, Institute of Biochemistry, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Miriam Klausberger
- Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Elisabeth Laurent
- Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria
- Core Facility Biomolecular & Cellular Analysis, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Maria Stadler
- Institute of Immunology, University of Veterinary Medicine, Vienna, Austria
| | - Gabriele Manhart
- Institute for Medical Biochemistry, University of Veterinary Medicine, Vienna, Austria
| | - Jasmin Huber
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria
| | - Manuela Hofner
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria
| | - Klemens Vierlinger
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria
| | - Andreas Weinhäusel
- Competence Unit Molecular Diagnostics, Center for Health and Bioresources, AIT Austrian Institute of Technology GmbH, Vienna, Austria
| | - Ines Swoboda
- Biotechnology Section, FH Campus Wien, University of Applied Sciences, Vienna, Austria
| | - Christoph J. Binder
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Wilhelm Gerner
- Institute of Immunology, University of Veterinary Medicine, Vienna, Austria
| | - Florian Grebien
- Institute for Medical Biochemistry, University of Veterinary Medicine, Vienna, Austria
| | - Friedrich Altmann
- Department of Chemistry, Institute of Biochemistry, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Lukas Mach
- Department of Applied Genetics and Cell Biology, Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Eva Stöger
- Department of Applied Genetics and Cell Biology, Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Richard Strasser
- Department of Applied Genetics and Cell Biology, Institute of Plant Biotechnology and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria
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Fuhrmann V, Huang HJ, Akarsu A, Shilovskiy I, Elisyutina O, Khaitov M, van Hage M, Linhart B, Focke-Tejkl M, Valenta R, Sekerel BE. From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack. Front Immunol 2021; 12:742732. [PMID: 34630424 PMCID: PMC8496898 DOI: 10.3389/fimmu.2021.742732] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 08/23/2021] [Indexed: 12/02/2022] Open
Abstract
Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.
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Affiliation(s)
- Verena Fuhrmann
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Huey-Jy Huang
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Aysegul Akarsu
- Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Igor Shilovskiy
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Olga Elisyutina
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Musa Khaitov
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - Marianne van Hage
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University, Hospital, Stockholm, Sweden
| | - Birgit Linhart
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Margarete Focke-Tejkl
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Karl Landsteiner University of Health Sciences, Krems, Austria
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Bulent Enis Sekerel
- Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
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Platts‐Mills TA, Hilger C, Jappe U, van Hage M, Gadermaier G, Spillner E, Lidholm J, Keshavarz B, Aalberse RC, van Ree R, Goodman RE, Pomés A. Carbohydrate epitopes currently recognized as targets for IgE antibodies. Allergy 2021; 76:2383-2394. [PMID: 33655520 DOI: 10.1111/all.14802] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 02/17/2021] [Accepted: 02/26/2021] [Indexed: 12/11/2022]
Abstract
Until recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub-Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE-binding glycans recognized up to 2008 were considered to be "classical" cross-reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE-binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose-alpha-1,3-galactose (alpha-gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha-gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross-reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub-Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website (www.allergen.org). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed.
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Affiliation(s)
- Thomas A. Platts‐Mills
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Division of Allergy and Immunology University of Virginia Charlottesville Virginia USA
| | - Christiane Hilger
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Department of Infection and Immunity Luxembourg Institute of Health Esch‐sur‐Alzette Luxembourg
| | - Uta Jappe
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Division of Clinical and Molecular Allergology, Research Center Borstel AirwayResearch Center North (ARCN)German Center for Lung Research Borstel Germany
- Interdisciplinary Allergy Outpatient Clinic, Department of Internal Medicine and Pneumology University of Lübeck Lübeck Germany
| | - Marianne van Hage
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Department of Medicine Solna, Division of Immunology and Allergy Karolinska Institutet & Karolinska University Hospital Stockholm Sweden
| | - Gabriele Gadermaier
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Department of Biosciences Paris Lodron University of Salzburg Salzburg Austria
| | - Edzard Spillner
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Department of Biological and Chemical Engineering Aarhus University Denmark
| | - Jonas Lidholm
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Thermo Fisher Scientific Uppsala Sweden
| | - Behnam Keshavarz
- Division of Allergy and Immunology University of Virginia Charlottesville Virginia USA
| | - Rob C. Aalberse
- Department of Immunopathology Sanquin Amsterdam The Netherlands
| | - Ronald van Ree
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Departments of Experimental Immunology and of Otorhinolaryngology Amsterdam University Medical Centers, Academic Medical Center Amsterdam The Netherlands
| | - Richard E. Goodman
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Food Allergy Research & Resource Program University of Nebraska Lincoln Nebraska USA
| | - Anna Pomés
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Basic Research, Indoor Biotechnologies, Inc. Charlottesville Virginia USA
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Engin A, Oktelik FB, Gelincik A, Sin A, Sin BA, Dursun BA, Beyaz S, Gorgulu B, Cetin E, Deniz G. The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice. Allergy Asthma Proc 2021; 42:350-356. [PMID: 34187627 DOI: 10.2500/aap.2021.42.210024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Background: Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy. Objective: In this study, the contribution of component-resolved diagnostics (CRD) is evaluated in the diagnosis of Hymenoptera venom allergy. Method: Ninety-three patients from four different centers in Turkey were included in the study. Conventional tests, including prick and intradermal skin tests, with commercial venom extracts and serum specific IgE (sIgE) levels for whole venoms were performed. An sIgE analysis for venom allergen components, including rApi m 1, rApi m 2, rApi m 10, rVes v 1, rVes v 5, were evaluated by immunoblotting. Results: In conventional test results, 17 of 35 patients with bee venom allergy were positive to honey bee venom, whereas 18 patients were positive to bee and wasp venoms. In 28 of 35 patients with bee venom allergy, the diagnosis was confirmed with CRD. CRD revealed a sensitivity of 80% in patients with bee venom allergy. According to conventional tests, 7 of 24 patients with vespid venom allergy demonstrated sensitivity only to Vespula species, whereas 17 patients revealed double positivity. The total diagnostic sensitivity of Ves v 1 and Ves v 5 was calculated as 87.5%. Ten of 23 patients with a history of hypersensitivity to both venoms showed double sensitivity with CRD; one patient had cross-reactivity, one patient was found to be sensitive only to bee venom, and, eight patients were sensitive only to Vespula species. Eleven patients had an uncertain history in terms of the culprit insect type and six of them had double sensitivity in CRD. Conclusion: CRD seemed to be more helpful in diagnosing vespid venom allergy than bee venom allergy. It can also discriminate clinically significant sensitizations from irrelevant ones.
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Affiliation(s)
- Ayse Engin
- From the Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Fatma B. Oktelik
- From the Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Aslı Gelincik
- Division of Allergy and Immunology, Department of Internal Medicine, Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Aytul Sin
- Division of Allergy and Immunology, Department of Internal Medicine, Ege University Faculty of Medicine, Izmir, Turkey
| | - Betul A. Sin
- Division of Immunology and Allergy, School of Medicine, Ankara University, Ankara, Turkey, and
| | - Berna A. Dursun
- Department of Immunology and Allergy Diseases, Recep Tayyip Erdogan University Faculty of Medicine, Training and Research Hospital, Rize, Turkey
| | - Sengul Beyaz
- Division of Allergy and Immunology, Department of Internal Medicine, Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Begum Gorgulu
- Division of Immunology and Allergy, School of Medicine, Ankara University, Ankara, Turkey, and
| | - Esin Cetin
- From the Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Gunnur Deniz
- From the Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
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30
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Wangorsch A, Jamin A, Eichhorn S, Pablos I, Sharma S, Schweidler B, Kastner B, Wildner S, Saloga J, Führer F, Reyna Orozco RR, Sherkat R, Sadeghi S, Teifoori F, Park JW, Briza P, Vieths S, Ferreira F, Arora N, Lidholm J, Gadermaier G, Scheurer S. Component-Resolved Diagnosis of American Cockroach (Periplaneta americana) Allergy in Patients From Different Geographical Areas. FRONTIERS IN ALLERGY 2021; 2:691627. [PMID: 35386988 PMCID: PMC8974670 DOI: 10.3389/falgy.2021.691627] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 06/03/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Manifestation of respiratory allergy to American cockroach (Periplaneta americana) is prominent in the subtropical and tropical areas. However, co-existing perennial indoor inhalant allergies frequently compromise clinical diagnosis of cockroach allergy, and the analysis of sensitization pattern is limited by the lack of Periplaneta allergens widely available for component-resolved diagnostics (CRD). Objective: To evaluate a collection of previously described recombinant Periplaneta allergens for CRD in cockroach allergy. Methods: A panel of nine recombinant Periplaneta allergens (Per a 1–5, 7–10) was generated, purified, and subjected to physicochemical characterization by applying circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), amino acid (AA) analysis, and mass spectrometry (MS). Patients (n = 117) from India, Korea, Venezuela, and Iran, reporting perennial respiratory indoor allergies with IgE sensitization to cockroach (P. americana and/or Blattella germanica), were included. The sensitization profile was monitored by the experimental ImmunoCAP testing. Results: ImmunoCAP testing confirmed IgE sensitization to Periplaneta and/or Blattella extract in 98 of 117 patients (r = 0.95). Five out of 117 patients were sensitized to only one of the two cockroach species. Within the whole study group, the prevalence of sensitization to individual allergens varied from 4% (Per a 2) to 50% (Per a 9), with the highest IgE values to Per a 9. Patients from four countries displayed different sensitization profiles at which Per a 3 and Per a 9 were identified as major allergens in India and Korea. Periplaneta-derived lipocalin and myosin light chain were characterized as new minor allergens, designated as Per a 4 and Per a 8. Periplaneta extract showed higher diagnostic sensitivity than all individual components combined, suggesting the existence of allergens yet to be discovered. Conclusion: Utilization of a panel of purified Periplaneta allergens revealed highly heterogeneous sensitization patterns and allowed the classification of lipocalin and myosin light chain from Periplaneta as new minor allergens.
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Affiliation(s)
| | - Annette Jamin
- Molecular Allergology, Paul-Ehrlich-Institut, Langen, Germany
| | - Stephanie Eichhorn
- Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria
| | - Isabel Pablos
- Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria
| | - Swati Sharma
- Allergy and Immunology Section, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India
| | - Bettina Schweidler
- Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria
| | - Bianca Kastner
- Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria
| | - Sabrina Wildner
- Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria
| | - Joachim Saloga
- Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Frank Führer
- Batch Control and Allergen Analysis, Paul-Ehrlich-Institut, Langen, Germany
| | | | - Roya Sherkat
- Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Somayeh Sadeghi
- Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fardis Teifoori
- Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Jung-Won Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Peter Briza
- Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria
| | - Stefan Vieths
- Molecular Allergology, Paul-Ehrlich-Institut, Langen, Germany
| | - Fatima Ferreira
- Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria
| | - Naveen Arora
- Allergy and Immunology Section, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India
| | - Jonas Lidholm
- Thermo Fisher Scientific, Immunodiagnostics, Uppsala, Sweden
| | - Gabriele Gadermaier
- Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria
| | - Stephan Scheurer
- Molecular Allergology, Paul-Ehrlich-Institut, Langen, Germany
- *Correspondence: Stephan Scheurer
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31
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Canning P, Brame B, Stefanovski D, Lee KW, Cain CL, Rook K, Morris DO. Multivariable analysis of the influence of cross-reactive carbohydrate determinant inhibition and other factors on intradermal and serological allergen test results: a prospective, multicentre study. Vet Dermatol 2021; 32:347-e96. [PMID: 34105194 DOI: 10.1111/vde.12974] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/27/2021] [Accepted: 02/13/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Serological allergen testing (SAT) is used widely to formulate allergen-specific immunotherapy for atopic dogs. Serum immunoglobulin (Ig)E specific for cross-reactive carbohydrate determinants (CCD) can produce false-positive reactions, creating discrepancy between SAT and intradermal allergen test (IDAT) results. OBJECTIVES The primary objective was to determine if inhibition of anti-CCD IgE in a commercial assay improved correlation with IDAT. The secondary objective was to assess the influence of dog- and clinic-specific factors, environmental factors, putative allergen exposure and prior medications on intradermal and SAT reactivity. ANIMALS Two-hundred and eleven client-owned dogs were enrolled from eight North American dermatology specialty practices. METHODS AND MATERIALS Collection of serum samples and IDAT were performed on the same day. Sera were assayed for detection of IgE specific to 25 allergens, before and after treatment with a proprietary inhibitor of anti-CCD IgE. Data for each dog were collected via a questionnaire filled out by veterinary personnel. RESULTS The correlation between the testing modalities was fair before (Spearman's rho, ρ = 0.2092) and after (ρ = 0.3042) inhibition of anti-CCD IgE. Ciclosporin dose (P = 0.003), independent of duration of use, and duration of lokivetmab use (P = 0.001), independent of dose administered, were associated with statistically significant decreases in IgE concentrations across all allergen types. CONCLUSIONS AND CLINICAL RELEVANCE Contrary to previous reports, this study demonstrated unchanged correlation between SAT and IDAT after inhibition of anti-CCD IgE. Ciclosporin dose and lokivetmab treatment duration may have unexplored effects on IgE concentration during SAT.
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Affiliation(s)
- Peter Canning
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, 3900 Spruce Street, Philadelphia, PA, 19104, USA
| | - Bailey Brame
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, 3900 Spruce Street, Philadelphia, PA, 19104, USA
| | - Darko Stefanovski
- Department of Clinical Studies - New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, 382 W Street Road, Kennett Square, PA, 19348, USA
| | - Kenneth W Lee
- Stallergenes Greer Laboratories, 639 Nuway Circle, Lenoir, NC, 28645, USA
| | - Christine L Cain
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, 3900 Spruce Street, Philadelphia, PA, 19104, USA
| | - Katherine Rook
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, 3900 Spruce Street, Philadelphia, PA, 19104, USA
| | - Daniel O Morris
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, 3900 Spruce Street, Philadelphia, PA, 19104, USA
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32
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Mohammaddavoodi A, Christian M, Müller E, Panakova L, Burgener I, Wagner R. Prevalence of immunoglobulin E against cross-reactive carbohydrate determinants and the impact of a blocker in canine sera. TIERAERZTLICHE PRAXIS AUSGABE KLEINTIERE HEIMTIERE 2021; 49:272-277. [PMID: 34005830 DOI: 10.1055/a-1442-3928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVE Cross-reactive carbohydrate determinants (CCD) cause multiple positive results in seasonal in vitro allergy tests. False positive/clinically irrelevant results have been identified due to the binding of immunoglobulin E against CCD (anti-CCD IgE) when testing for pollen allergens. The aim of this study was to investigate the prevalence of polysensitised serum samples and evaluate the impact of a CCD inhibitor/blocker in seasonal allergy test results. MATERIAL AND METHODS A total of 4614 canine serum samples, submitted from July 2017 to June 2018 for seasonal in vitro allergy test via ELISA Fc-Ε receptor technology, were studied. Samples were grouped into polysensitised (group A) and non-polysensitised (group B). Polysensitised samples were retested after adding a modified glycoprotein plant extract (blocker). To determine the impact of the blocker for each allergen, results prior and post blocking were investigated in 96 randomly selected samples. RESULTS Polysensitisation to seasonal allergens was diagnosed in 818 (17.7 %) serum samples. The blocker eliminated the binding of anti-CCD IgE to allergen extracts (49 %) or suppressed the reaction classes (40 %) which are indicative of the presence of clinically relevant IgE. Negative reactions after blocking were less common when testing for antibodies against a mixture of 6-grass mix (29 %), rye (22 %), and sheep sorrel (20 %) in comparison to nettle (82 %), willow (70 %), birch-hazel (65 %), mugwort-ragweed (63 %) and English plantain (57 %). CONCLUSION AND CLINICAL RELEVANCE Blocking should be used in the case of polysensitized results to improve the quality of seasonal in vitro allergy tests and avoid the use of allergen-specific immunotherapy (ASIT) for clinically irrelevant allergens.
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Affiliation(s)
| | - Maria Christian
- Laboklin laboratory for clinical diagnostics GMBH & CO. KG, Bad Kissingen, Germany
| | - Elisabeth Müller
- Laboklin laboratory for clinical diagnostics GMBH & CO. KG, Bad Kissingen, Germany
| | - Lucia Panakova
- Clinic of Internal Medicine Small Animals, Department for Companion Animals and Horses, Vetmeduni Vienna, Vienna, Austria
| | - Iwan Burgener
- Clinic of Internal Medicine Small Animals, Department for Companion Animals and Horses, Vetmeduni Vienna, Vienna, Austria
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Enck KM, Lee KW, McKinney BH, Blankenship KD, Montesano C. Detection and inhibition of IgE antibodies reactive with cross-reactive carbohydrate determinants in an ELISA for allergen-specific IgE in horses. Vet Dermatol 2021; 32:685-e184. [PMID: 33956389 DOI: 10.1111/vde.12963] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 01/29/2021] [Accepted: 02/09/2021] [Indexed: 01/25/2023]
Abstract
BACKGROUND It has been demonstrated that immunoglobulin (Ig)E specific for cross-reactive carbohydrate determinants (CCD) is present in the serum of sensitized humans, dogs and cats, and that these CCD-specific antibodies might confound serological testing. HYPOTHESIS/OBJECTIVE The objective was to determine whether or not CCD-reactive antibodies occur in horses and to investigate the prevalence of CCD-reactive IgE antibodies in equine sera using a monoclonal cocktail-based enzyme-linked immunosorbent assay designed to detect allergen-specific IgE in horses, and to evaluate a means for successful inhibition of these CCD. METHODS AND MATERIALS Sera from 28 horses suspected of clinical allergy were evaluated, with and without a proprietary inhibitor which contains carbohydrates derived from bromelain (BROM-CCD), using a panel of 72 allergens that include 15 grasses, 17 trees, nine weeds, five mites, 12 fungi, 12 insects and two environmental allergens. RESULTS Twenty-five samples were shown to be reactive to at least one of the allergens, and 15 were reactive to 10 allergens or more. BROM-CCD had minimal effect on the mite reactivity in any of the positive samples; however, substantial inhibition for pollen allergens (trees, grasses and weeds) was demonstrable. Reduction in signal to pollens ranged from 20% to 100% for samples that were inhibited by CCD-BROM. CONCLUSIONS AND CLINICAL IMPORTANCE These results demonstrate that CCD-reactive IgE antibodies are evident in horses and that BROM-CCD can be effective in reducing reactions with these irrelevant carbohydrates and will likely yield a more accurate in vitro allergen reactivity profile for selection of allergens included in an immunotherapeutic regime.
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Affiliation(s)
- Kevin M Enck
- Stallergenes Greer, 639 Nuway Circle, Lenoir, NC, USA
| | - Kenneth W Lee
- Stallergenes Greer, 639 Nuway Circle, Lenoir, NC, USA
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Md A, Maeda M, Matsui T, Takasato Y, Ito K, Kimura Y. Purification and molecular characterization of a truncated-type Ara h 1, a major peanut allergen: oligomer structure, antigenicity, and glycoform. Glycoconj J 2021; 38:67-76. [PMID: 33439436 DOI: 10.1007/s10719-020-09969-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 12/11/2020] [Accepted: 12/23/2020] [Indexed: 11/29/2022]
Abstract
Peanut allergies are among the most severe food allergies, and several allergenic proteins referred to as Ara h 1-Ara h 17 have been identified from peanut seeds. The molecular characterization of Ara h 1 (63 kDa), a glycosylated allergen, has almost been completed, and the occurrence of two homologous genes (clone 41B and clone P17) has been identified. In this study, we found a new variant of Ara h 1 i.e. 54 kDa, in which the N-terminal amino acid sequence was EGREGEQ-, indicating that the N-terminal domain of 63 kDa Ara h 1 had been removed. This new isoform was obtained from the run-through fraction of hydrophobic interaction chromatography while 63 kDa Ara h 1 was tightly bound to the hydrophobic resins, suggesting that the removal of the N-terminal domain resulted in extreme hydrophilic properties. We found that 63 kDa Ara h 1 occurs as higher order homo-oligomeric conformations such as decamer or nonamer, while 54 kDa Ara h 1 occurs exclusively as a homotrimer, indicating that the N-terminal domain of the 63 kDa molecule may be involved in higher order oligomerization. When antisera from peanut-allergic patients were treated with both the Ara h 1 molecules, the immunoglobulin E (IgE) antibodies in these sera reacted with each Ara h 1 molecule, suggesting that the C-terminal as well as the N-terminal domains of Ara h 1 contribute significantly to the epitope formations of this peanut glycoallergen. Furthermore, the glycoform analyses of N-glycans linked to 63 kDa and 54 kDa Ara h 1 subunits revealed that both typical high-mannose type and β-xylosylated type N-glycans are linked to the molecules. The cross-reactivity of IgE against Ara h 1 in the serum of one peanut allergy patient was completely lost by de-N-glycosylation, indicating the N-glycan of Ara h 1 was the sole epitope for the Ara h 1- specific IgE in the patient.
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Affiliation(s)
- Asaduzzaman Md
- Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-Naka, Okayama, 700-8530, Japan
| | - Megumi Maeda
- Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-Naka, Okayama, 700-8530, Japan
| | - Teruaki Matsui
- Department of Allergy, Aichi Children's Health and Medical Center, 7-426, Obu, Morioka, Aichi, 474-8710, Japan
| | - Yoshihiro Takasato
- Department of Allergy, Aichi Children's Health and Medical Center, 7-426, Obu, Morioka, Aichi, 474-8710, Japan
| | - Komei Ito
- Department of Allergy, Aichi Children's Health and Medical Center, 7-426, Obu, Morioka, Aichi, 474-8710, Japan
| | - Yoshinobu Kimura
- Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-Naka, Okayama, 700-8530, Japan.
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Keshavarz B, Platts-Mills TAE, Wilson JM. The use of microarray and other multiplex technologies in the diagnosis of allergy. Ann Allergy Asthma Immunol 2021; 127:10-18. [PMID: 33450398 DOI: 10.1016/j.anai.2021.01.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/18/2020] [Accepted: 01/04/2021] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To give an overview and describe the strengths and weaknesses of immunoglobulin E (IgE) microarray and other multiplex assays that have been developed and are being used for allergy diagnostics. DATA SOURCES Queries for IgE microarray and multiplex assays were conducted with PubMed and Google Scholar, searching for primary articles and review papers. STUDY SELECTIONS We focused on articles written in English on commercially available IgE multiplex assays that were reported in the allergy and immunology literature. RESULTS Several commercial IgE assays that use microarray or other multiplex technology have been developed, and some have been implemented into clinical practice in Europe and Asia, with the Immuno Solid-Phase Allergen Chip being the most widely studied. Results of these assays generally correlate with results using "singleplex" IgE assays (eg, ImmunoCAP), though there can be variability among products and among allergens. A strength of the microarray technology is that IgE to a large number of allergens can be detected simultaneously in a single test, and only a small amount of patient serum is required. Cost, inadequate sensitivity under some scenarios, and difficulties with data interpretation, in some cases of 100 or more allergens, can be limitations. CONCLUSION IgE microarray assays are already a valuable tool in research applications. These assays, and also other forms of IgE multiplex assays, are likely to play an important role in the clinical practice of allergy in the future. Additional studies focused on clinical outcomes, and the development of more targeted allergen panels could facilitate increased clinical use.
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Affiliation(s)
- Behnam Keshavarz
- Division of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, Virginia
| | - Thomas A E Platts-Mills
- Division of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, Virginia
| | - Jeffrey M Wilson
- Division of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, Virginia.
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Casas ML, Esteban Á, González-Muñoz M, Labrador-Horrillo M, Pascal M, Teniente-Serra A. Proyecto VALIDA: Validation of ALlergy In vitro Diagnostics Assays (Herramientas y recomendaciones para la valoración de las pruebas in vitro en el diagnóstico de la alergia). ADVANCES IN LABORATORY MEDICINE 2020; 1:20200022. [PMCID: PMC10197503 DOI: 10.1515/almed-2020-0022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 05/05/2020] [Indexed: 08/29/2023]
Abstract
En la evaluación del paciente con sospecha de alergia las pruebas de detección y cuantificación de la inmunoglobulina E (IgE) específica in vitro se usan de manera habitual en los laboratorios clínicos para ayudar en el diagnóstico de la alergia. Actualmente existen diferentes alternativas comerciales para realizar estos ensayos, pero los resultados obtenidos por cada uno de ellos pueden variar, lo que condiciona el diagnóstico y el tratamiento que se le proporcionará al paciente. Con el fin de dar respuesta a los retos planteados por las diferencias entre las distintas técnicas para la determinación in vitro de la IgE específica, un grupo de expertos ha recogido en un documento una serie de recomendaciones sobre las implicaciones que puede tener el uso de una determinada técnica in vitro y el impacto en el manejo del paciente alérgico que suponen las diferencias entre las distintas técnicas. La lectura y el análisis de este documento de consenso ayudarán a entender las implicaciones que tiene el cambio de método de diagnóstico in vitro en el manejo del paciente con alergia, en su calidad de vida y en los costes socioeconómicos asociados a la enfermedad.
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Affiliation(s)
- María L. Casas
- Sociedad Española de Medicina de Laboratorio (SEQC-ML), Barcelona, España
- Servicio de Análisis Clínicos, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, España
| | - Ángel Esteban
- Sociedad Española de Medicina de Laboratorio (SEQC-ML), Barcelona, España
- Servicio de Análisis Clínicos, Hospital General Universitario de Alicante, Alicante, España
| | - Miguel González-Muñoz
- Sociedad Española de Inmunología (SEI), Barcelona, España
- Servicio de Inmunología, Hospital Universitario La Paz, Madrid, España
| | - Moisés Labrador-Horrillo
- Sociedad Española de Alergología e Inmunología Clínica (SEAIC), Madrid, España
- Servicio de Alergología, Hospital Universitari Vall d’Hebron, Barcelona, España
| | - Mariona Pascal
- Servicio de Alergología, Hospital Universitari Vall d’Hebron, Barcelona, España
- Servicio de Inmunología, CDB, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, España
- Red de Investigación ARADyAL, Instituto Carlos III, Madrid, España
| | - Aina Teniente-Serra
- Sociedad Española de Inmunología (SEI), Barcelona, España
- Servicio de Inmunología, LCMN, Hospital Universitari Germans Trias i Pujol, Badalona, España
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Mohammaddavoodi A, Panakova L, Christian M, Burgener I, Müller E, Wagner R. [Prevalance of immunoglobulin E against cross-reactive carbohydrate determinants (CCD) and impact of a blocker in seasonal allergy tests]. TIERAERZTLICHE PRAXIS AUSGABE KLEINTIERE HEIMTIERE 2020; 48:404-409. [PMID: 33276390 DOI: 10.1055/a-1274-9188] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
OBJECTIVES Cross-reactive carbohydrate determinants (CCD) cause false positive/clinically irrelevant results in seasonal in vitro allergy tests due to the binding of immunoglobulin IgE against CCD (anti-CCD IgE).There is no study regarding the presence of this phenomen in cats. The aim of this study was to investigate the prevalence of polysensitization in serum samples and evaluate the impact of a CCD inhibitor/blocker in multi-positive seasonal allergy test results in cats. MATERIALS AND METHODS A total of 472 feline sera, submitted from July 2017 to June 2018 for seasonal in vitro allergy test via ELISA Fc-Ε receptor technology, were studied. Samples were grouped into polysensitized (group A) and non-polysensitized (group B). Polysensitized samples (A) were retested after adding a modified glycoprotein plants extract (blocker). To determine the impact of the blocking to each allergen, the results in 48 randomly selected samples in cats prior- and post-blocking were investigated. RESULTS Polysensitization to seasonal allergens was diagnosed in 137 (29 %) samples. No discrepancy in presence of polysensitization was seen in different seasons. Blocking eliminated the binding of anti-CCD IgE and produced either negative test results (49 %) or a decrease of 1-4 reaction classes (41 %) which is indicative of the simultaneous presence of clinically relevant allergen specific IgE. Total negative reactions after blocking were less common in 6-grass mix (31 %), rye (23 %) and sheep sorrel (25 %) in comparison to willow und birch-hazel (67 %), mugwort-ragweed und nettle (65 %), as well as English plantain (54 %). CONCLUSION AND CLINICAL RELEVANCE In order to improve the quality of seasonal in vitro allergy test, blocking should be employed in cases of polysensitized results resulting in an avoidance of the administration of non-offending allergens during allergen-specific immunotherapy (ASIT).
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Affiliation(s)
| | - Lucia Panakova
- Klinik für Interne Medizin Kleintiere, Department für Kleintiere und Pferde der Veterinärmedizinischen Universität Wien
| | | | - Iwan Burgener
- Klinik für Interne Medizin Kleintiere, Department für Kleintiere und Pferde der Veterinärmedizinischen Universität Wien
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Lee KW, McKinney BH, Blankenship KD, Morris DO. Detection and Inhibition of IgE for cross-reactive carbohydrate determinants evident in an enzyme-linked immunosorbent assay for detection of allergen-specific IgE in the sera of dogs and cats. Vet Dermatol 2020; 31:439-e116. [PMID: 32975354 PMCID: PMC7756665 DOI: 10.1111/vde.12904] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND It has been demonstrated recently that immunoglobulin (Ig)E specific for cross-reactive carbohydrate determinants (CCD) is present in the serum of allergen-sensitized dogs and cats, and that these CCD-specific antibodies might confound serological testing. HYPOTHESIS/OBJECTIVE The objective was to document the prevalence of CCD detectable in a monoclonal cocktail-based enzyme-linked immunosorbent assay designed for the detection of allergen-specific IgE in the sera of dogs and cats, and to define a means for successful inhibition of these CCD. METHODS AND MATERIALS The incidence of reactivity to bromelain and a commercially available inhibitor of carbohydrate-specific antibodies (RIDA-CCD) was evaluated in 100 dog sera samples before and after inhibition with RIDA-CCD and a proprietary inhibitor containing carbohydrates derived from bromelain (BROM-CCD). Subsequently, sera from 600 dogs and 600 cats were evaluated using a serum diluent with and without BROM-CCD. RESULTS Both the RIDA-CCD and BROM-CCD inhibitors demonstrated successful reduction of CCD reactivity, although a more efficient profile of inhibition was evident with BROM-CCD. Mite reactivity in dog and cat sera was largely unaffected; however, substantial inhibition for pollen allergens (trees, grasses and weeds) was shown. After BROM-CCD inhibition, 1% of canine samples and 13% of feline samples were rendered completely negative for allergen reactivity. CONCLUSIONS AND CLINICAL IMPORTANCE The results demonstrate that BROM-CCD is effective in reducing reactions with irrelevant carbohydrates, and that inhibition of CCD reactivity might substantially alter the outcome of the in vitro reactivity profile used for selection of allergens to be included in an immunotherapeutic regime.
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Affiliation(s)
| | | | | | - Daniel O. Morris
- School of Veterinary MedicineUniversity of Pennsylvania3900 Spruce StPhiladelphiaPA19104USA
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Casas ML, Esteban Á, González-Muñoz M, Labrador-Horrillo M, Pascal M, Teniente-Serra A. VALIDA project: Validation of allergy in vitro diagnostics assays (Tools and recommendations for the assessment of in vitro tests in the diagnosis of allergy). ADVANCES IN LABORATORY MEDICINE 2020; 1:20200051. [PMID: 37360620 PMCID: PMC10197418 DOI: 10.1515/almed-2020-0051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 05/05/2020] [Indexed: 06/28/2023]
Abstract
In vitro allergen-specific immunoglobulin E (IgE) detection and quantification tests are routinely performed in clinical laboratories to diagnose patients with a suspected allergy. Numerous commercial assays are available to test for allergies, but the results can vary widely, thereby influencing both diagnosis and treatment. Given the challenges posed by differences in the various assays for in vitro determination of specific IgE, a group of experts has compiled in a document a series of recommendations on the implications that the use of a certain in vitro technique may have and the impact on the management of the allergic patient that the differences between the various techniques represent. The reading and analysis of this consensus document will help to understand the implications of the change of in vitro diagnostic method in the management of the patient with allergy, in the quality of life and in the socioeconomic costs associated with the disease.
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Affiliation(s)
- María L. Casas
- Clinical Analysis Service, Fundación Alcorcón University Hospital, Alcorcón, Madrid, Spain
- Spanish Society of Laboratory Medicine (SEQC-ML), Barcelona, Spain
| | - Ángel Esteban
- Spanish Society of Laboratory Medicine (SEQC-ML), Barcelona, Spain
- Clinical Analysis Service, University General Hospital of Alicante, Alicante, Spain
| | - Miguel González-Muñoz
- Immunology Service, La Paz University Hospital, Madrid, Spain
- Spanish Society of Immunology (SEI), Barcelona, Spain
| | - Moisés Labrador-Horrillo
- Allergology Service, Vall d’Hebron University Hospital, Barcelona, Spain
- Spanish Society of Allergology and Clinical Immunology (SEAIC), Madrid, Spain
| | - Mariona Pascal
- Spanish Society of Immunology (SEI), Barcelona, Spain
- Spanish Society of Allergology and Clinical Immunology (SEAIC), Madrid, Spain
- Immunology Service, CBD, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain
- ARADyAL Research Network, Carlos III Institute, Madrid, Spain
| | - Aina Teniente-Serra
- Spanish Society of Immunology (SEI), Barcelona, Spain
- Immunology Service, LCMN, Germans Trias i Pujol University Hospital, Badalona, Spain
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Bergmann-Hug K, Fricker M, Hausmann O, Helbling A, Jörg L. Sensitization to Hymenoptera venom in pollen allergic patients: Frequency and involvement of cross-reacting carbohydrate determinants (CCD). PLoS One 2020; 15:e0238740. [PMID: 32898145 PMCID: PMC7478646 DOI: 10.1371/journal.pone.0238740] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 08/21/2020] [Indexed: 01/26/2023] Open
Abstract
Sensitization to Hymenoptera venom in patients without a history of systemic allergic reactions to Hymenoptera stings is frequently found and can be due to the presence of specific IgE to cross-reactive carbohydrate determinants (CCD). This study investigates 105 pollen allergic subjects for the presence of specific IgE to honeybee or wasp venom, pollen, the MUXF3 carbohydrate epitope from bromelain and recombinant Hymenoptera venom components. In addition, in a subgroup of patients (n = 10) a basophil activation test (BAT) using bee and wasp venom was performed. Specific IgE to Hymenoptera venom was detected in 45.7% of the pollen allergic subjects and in 26.7% of the non-atopic controls, both without a history of systemic allergic reactions to Hymenoptera stings. The high sensitization rate in atopic patients could partially be explained by cross-sensitization between pollen and Hymenoptera venom due to specific IgE to CCDs. In our study population, only 20% showed a sensitization to CCDs. Primary sensitization due to sting exposure, high total IgE values or unspecific binding and detection of low affinity antibodies in the test procedure could be reasons. Thus, determination of specific IgE to Hymenoptera venom in patients without a history of systemic allergic reactions as screening test is not recommended.
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Affiliation(s)
- Katrin Bergmann-Hug
- Allergy Unit, Zieglerspital, Clinic of Internal Medicine, Spital Netz Bern AG, Bern, Switzerland
- Department of Rheumatology, Immunology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Michael Fricker
- Department of Rheumatology, Immunology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Praxisgemeinschaft Mörigen, Mörigen, Switzerland
| | - Oliver Hausmann
- Department of Rheumatology, Immunology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- ADR-AC GmbH, Adverse Drug Reactions, Analysis and Consulting, Bern, Switzerland
- Löwenpraxis Luzern, Lucerne, Switzerland
| | - Arthur Helbling
- Allergy Unit, Zieglerspital, Clinic of Internal Medicine, Spital Netz Bern AG, Bern, Switzerland
- Department of Rheumatology, Immunology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Lukas Jörg
- Department of Rheumatology, Immunology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- * E-mail:
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Sabit M, Wong C, Andaya A, Ramos JD. Pollen allergen skin test and specific IgE reactivity among Filipinos: a community-based study. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2020; 16:74. [PMID: 32922458 PMCID: PMC7477877 DOI: 10.1186/s13223-020-00471-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 08/05/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND Despite the clinical importance of pollen allergens among Filipinos, few studies delve into the sensitization profiles of Filipinos against pollen allergens. This study determined the sensitization profile of Filipinos to pollen using skin prick test (SPT) and pollen-specific ELISA. METHODS Pollen from fifteen selected plant sources was collected and extracted for use in sensitization tests. Volunteers were interviewed for their clinical history prior to blood sampling and SPT. The blood samples collected were assessed using Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS The best panel of pollen allergens for the skin prick test was Mangifera indica (64%), Acacia auriculiformis (28%), Mimosa spp. (25%) Amaranthus spinosus (22%), Lantana camara (20%), Pilea microphylla (16%) and Dichanthium aristatum (15%). Young adults had more sensitizations to pollen than among early childhood and elderly. There were more allergic subjects that have rhinitis (61%) than asthma (42%) and atopic dermatitis (35%). Pollen-specific IgE levels show low percent reactivity as compared to the skin test with Cocos nucifera obtaining the highest IgE reactivity (21%). CONCLUSIONS Pollen allergens from both arboreal and herbaceous plants used in this study yielded positive reactivities for both skin tests and specific IgE tests.
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Affiliation(s)
- Maureen Sabit
- The Graduate School, University of Santo Tomas, 1008 Manila, Philippines
- Research Center for the Natural and Applied Sciences, Thomas Aquinas Research Complex, University of Santo Tomas, 1008 Manila, Philippines
- Department of Biological Sciences, College of Science, University of Santo Tomas, 1008 Manila, Philippines
| | - Cecil Wong
- Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Santo Tomas Hospital, 1008 Manila, Philippines
| | - Agnes Andaya
- Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Santo Tomas Hospital, 1008 Manila, Philippines
| | - John Donnie Ramos
- The Graduate School, University of Santo Tomas, 1008 Manila, Philippines
- Research Center for the Natural and Applied Sciences, Thomas Aquinas Research Complex, University of Santo Tomas, 1008 Manila, Philippines
- Department of Biological Sciences, College of Science, University of Santo Tomas, 1008 Manila, Philippines
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Matricardi PM. IgE to cross-reactive carbohydrate determinants: Origins, functions, and confounding role in nPhl p 4-IgE assays. J Allergy Clin Immunol 2020; 145:1554-1555. [PMID: 32507231 DOI: 10.1016/j.jaci.2020.04.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 04/07/2020] [Accepted: 04/09/2020] [Indexed: 11/29/2022]
Affiliation(s)
- Paolo Maria Matricardi
- Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
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Sinson E, Ocampo C, Liao C, Nguyen S, Dinh L, Rodems K, Whitters E, Hamilton RG. Cross-reactive carbohydrate determinant interference in cellulose-based IgE allergy tests utilizing recombinant allergen components. PLoS One 2020; 15:e0231344. [PMID: 32324770 PMCID: PMC7179882 DOI: 10.1371/journal.pone.0231344] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 03/21/2020] [Indexed: 12/21/2022] Open
Abstract
Background Cross-reactive carbohydrate determinant (CCD) structures found in plant and insect glycoproteins are commonly recognized by IgE antibodies as epitopes that can lead to extensive cross-reactivity and obscure in vitro diagnostic (IVD) serology results. With the introduction of component resolved diagnosis (CRD), recombinant non-glycosylated components have been utilized to mitigate the risk of CCD-specific IgE (sIgE) detection. However, a recent study has shown that CCD-sIgE may bind directly to the cellulose solid phase matrix used in certain in vitro diagnostic assays, eliminating the advantage of CRD over traditional extract-based testing. The aim of this study is to further investigate the prevalence of CCD-sIgE interference on a commonly-used in vitro sIgE automated platform which employs a cellulose-based matrix to immobilize CCD-free recombinant components. Methods Sera from patients sensitized to peanut, silver birch, and/or timothy grass were analyzed for CCD-sIgE reactivity on ImmunoCAP/Phadia and NOVEOS autoanalyzers against the MUXF3 carbohydrate component. Positive CCD-sIgE sera were further analyzed against non-glycosylated recombinant components bound to the ImmunoCAP solid phase in the absence and presence of a soluble CCD inhibitor. For comparison, sera were then analyzed on NOVEOS, a non-cellulose based automated sIgE assay. Results Sera from 35% of the sensitized population tested in this study were positive (≥0.35 kU/L) for CCD-sIgE. Of those positives, 17% resulted in CCD-sIgE-positive (false positive) results on ImmunoCAP using non-glycosylated allergosorbents that were negative on NOVEOS. Sera producing false-positive results on ImmunoCAP had varying levels of CCD-sIgE from 0.67 kU/L to 36.52 kU/L. The incidence of CCD interference was predominantly delimited to low-positive IgE results (0.35 kUA/L– 3.00 kUA/L). Conclusion Falsely elevated diagnostic allergen-sIgE results can commonly occur due to the presence of CCD-sIgE using assays that employ a carbohydrate matrix-based allergosorbent. Even the use of non-glycosylated recombinant allergenic components coupled to cellulose matrices do not reduce their risk of detection. The risk of CCD interference that compromises quantitative IgE results can be mitigated by the addition of a soluble CCD inhibitor to positive CCD-sIgE containing sera or by alternatively using a non-cellulose based sIgE assay, such as the NOVEOS assay.
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Affiliation(s)
- Edsel Sinson
- HYCOR Biomedical LLC, Garden Grove, California, United States of America
- * E-mail:
| | - Camille Ocampo
- HYCOR Biomedical LLC, Garden Grove, California, United States of America
| | - Cindy Liao
- HYCOR Biomedical LLC, Garden Grove, California, United States of America
| | - Steven Nguyen
- HYCOR Biomedical LLC, Garden Grove, California, United States of America
| | - Lauren Dinh
- HYCOR Biomedical LLC, Garden Grove, California, United States of America
| | - Kelline Rodems
- HYCOR Biomedical LLC, Garden Grove, California, United States of America
| | - Eric Whitters
- HYCOR Biomedical LLC, Garden Grove, California, United States of America
| | - Robert G. Hamilton
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
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Chamberlain P, Rup B. Immunogenicity Risk Assessment for an Engineered Human Cytokine Analogue Expressed in Different Cell Substrates. AAPS JOURNAL 2020; 22:65. [PMID: 32291556 DOI: 10.1208/s12248-020-00443-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 03/02/2020] [Indexed: 11/30/2022]
Abstract
The purpose of this article is to illustrate how performance of an immunogenicity risk assessment at the earliest stage of product development can be instructive for critical early decision-making such as choice of host system for expression of a recombinant therapeutic protein and determining the extent of analytical characterization and control of heterogeneity in co- and post-translational modifications. Application of a risk-based approach for a hypothetical recombinant DNA analogue of a human endogenous cytokine with immunomodulatory functions is described. The manner in which both intrinsic and extrinsic factors could interact to influence the relative scale of risk associated with expression in alternative hosts, namely Chinese hamster ovary (CHO) cells, Pichia pastoris, Escherichia coli, or Nicotinia tabacum is considered in relation to the development of the investigational product to treat an autoimmune condition. The article discusses how particular product-related variants (primary amino acid sequence modifications and post-translational glycosylation or other modifications) and process-derived impurities (host cell proteins, endotoxins, beta-glucans) associated with the different expression systems might influence the impact of immunogenicity on overall clinical benefit versus risk for a therapeutic protein candidate that has intrinsic MHC Class II binding potential. The implications of the choice of expression system for relative risk are discussed in relation to specific actions for evaluation and measures for risk mitigation, including use of in silico and in vitro methods to understand intrinsic immunogenic potential relative to incremental risk associated with non-human glycan and protein impurities. Finally, practical guidance on presentation of this information in regulatory submissions to support clinical development is provided.
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Affiliation(s)
- Paul Chamberlain
- NDA Advisory Board, NDA Regulatory Science Ltd, Grove House, Guildford Road, Leatherhead, Surrey, KT22 9DF, UK.
| | - Bonita Rup
- Bonnie Rup Consulting, LLC, Reading, Massachusetts, USA
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Park Y, Kim D, Boorgula GD, De Schutter K, Smagghe G, Šimo L, Archer-Hartmann SA, Azadi P. Alpha-Gal and Cross-Reactive Carbohydrate Determinants in the N-Glycans of Salivary Glands in the Lone Star Tick, Amblyomma americanum. Vaccines (Basel) 2020; 8:E18. [PMID: 31936588 PMCID: PMC7157712 DOI: 10.3390/vaccines8010018] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 12/20/2019] [Accepted: 12/20/2019] [Indexed: 12/11/2022] Open
Abstract
Ticks are important ectoparasites and vectors of numerous human and animal pathogens. Ticks secrete saliva that contains various bioactive materials to evade the host defense system, and often facilitates the pathogen transmission. In addition, the Lone star tick saliva is thought to be the sensitizer in red meat allergy that is characterized by an allergic reaction to glycan moieties carrying terminal galactose-alpha-1,3-galactose (aGal). To assess N-glycome of Amblyomma americanum, we examined the N-glycan structures in male and female salivary glands at three different feeding stages and in carcasses of partially fed lone star ticks. We also surveyed the genes involved in the N-glycosylation in the tick species. The aGal epitopes and cross-reactive carbohydrate determinants (CCD) increases over time after the onset of blood feeding in both male and female A. americanum. These CCDs include xylosylation of the core mannose, 1,3-mono and 1,3- and 1,6-difucosylations of the basal GlcNac and mono- or diantennary aGal. Combinations of both xylosylation and aGal and fucosylation and aGal were also found on the N-glycan structures. While the enzymes required for the early steps of the N-glycosylation pathway are quite conserved, the enzymes involved in the later stages of N-glycan maturation in the Golgi apparatus are highly diverged from those of insects. Most of all, we propose that the aGal serves as a molecular mimicry of bioactive proteins during tick feedings on mammalian hosts, while it contributes as a sensitizer of allergy in atypical host human.
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Affiliation(s)
- Yoonseong Park
- Department of Entomology, Kansas State University, Manhattan, KS 66506, USA; (D.K.); (G.D.B.)
| | - Donghun Kim
- Department of Entomology, Kansas State University, Manhattan, KS 66506, USA; (D.K.); (G.D.B.)
- Department of Applied Biology, Kyungpook National University, Sangju 37224, Gyeongbuk, Korea
| | - Gunavanthi D. Boorgula
- Department of Entomology, Kansas State University, Manhattan, KS 66506, USA; (D.K.); (G.D.B.)
| | - Kristof De Schutter
- Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium; (K.D.S.); (G.S.)
| | - Guy Smagghe
- Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium; (K.D.S.); (G.S.)
| | - Ladislav Šimo
- UMR BIPAR, INRAE, Ecole Nationale Vétérinaire d’Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, France;
| | | | - Parastoo Azadi
- Complex Carbohydrate Center, University of Georgia, Athens, GA 30602, USA; (S.A.A.-H.); (P.A.)
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Chan SK, Pomés A, Hilger C, Davies JM, Mueller G, Kuehn A, Lopata AL, Gadermaier G, van Hage M, Raulf M, Goodman RE. Keeping Allergen Names Clear and Defined. Front Immunol 2019; 10:2600. [PMID: 31798576 PMCID: PMC6878850 DOI: 10.3389/fimmu.2019.02600] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/21/2019] [Indexed: 12/23/2022] Open
Abstract
The World Health Organization/International Union of Immunological Societies (WHO/IUIS) Allergen Nomenclature Sub-Committee was established in 1986 by leading allergists to standardize names given to proteins that cause IgE-mediated reactions in humans. The Sub-Committee's objective is to assign unique names to allergens based on a critical analysis of confidentially submitted biochemical and clinical data from researchers, often prior to publication to preserve consistency. The Sub-Committee maintains and revises the database as the understanding of allergens evolves. This report summarizes recent developments that led to updates in classification of cockroach group 1 and 5 allergens to animal as well as environmental and occupational allergens. Interestingly, routes, doses, and frequency of exposure often affects allergenicity as does the biochemical properties of the proteins and similarity to self and other proteins. Information required by the Sub-Committee now is more extensive than previously as technology has improved. Identification of new allergens requires identification of the amino acid sequence and physical characteristics of the protein as well as demonstration of IgE binding from subjects verified by described clinical histories, proof of the presence of the protein in relevant exposure substances, and demonstration of biological activity (skin prick tests, activation of basophils, or mast cells). Names are assigned based on taxonomy with the abbreviation of genus and species and assignment of a number, which reflects the priority of discovery, but more often now, the relationships with homologous proteins in related species.
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Affiliation(s)
- Sanny K Chan
- Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, CO, United States
| | - Anna Pomés
- INDOOR Biotechnologies, Inc. Charlottesville, VA, United States
| | - Christiane Hilger
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Janet M Davies
- Centre for Children's Health Research, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.,Metro North Hospital and Health Service, Brisbane, QLD, Australia
| | - Geoffrey Mueller
- National Institute of Environmental Health Sciences, Durham, NC, United States
| | - Annette Kuehn
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Andreas L Lopata
- Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia
| | | | - Marianne van Hage
- Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet and University Hospital, Solna, Sweden
| | - Monika Raulf
- Institute of Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universitat Bochum, Bochum, Germany
| | - Richard E Goodman
- Food Allergy Research and Resource Program, Deptartment of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, OR, United States
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Piccione ML, DeBoer DJ. Serum IgE against cross-reactive carbohydrate determinants (CCD) in healthy and atopic dogs. Vet Dermatol 2019; 30:507-e153. [PMID: 31642119 DOI: 10.1111/vde.12799] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2019] [Indexed: 01/09/2023]
Abstract
BACKGROUND Cross-reactive carbohydrate determinants (CCD) are Immunoglobulin E (IgE)-binding carbohydrate structures common to plant and insect species. In people, anti-CCD IgE is thought to be clinically irrelevant, but to have the potential to confound serological IgE test interpretations. Previous studies reported the detection of anti-CCD IgE in 24-73% of atopic dog sera; prevalence in healthy dogs has not been reported. OBJECTIVE To compare the prevalence of anti-CCD IgE in a group of healthy and atopic dogs. ANIMALS Sera from 61 healthy dogs and 101 dogs with a clinical diagnosis of atopic dermatitis were analyzed for IgE against CCD. METHODS AND MATERIALS Sera were analyzed for the presence of anti-CCD IgE and IgE against environmental allergens using a commercial multiplex allergen-specific IgE assay. RESULTS Anti-CCD IgE was detected in 17 of 101 (16.8%) atopic dog sera and eight of 61 (13.1%) healthy dog sera (P = 0.65, Fisher's exact test). All healthy and atopic dogs with anti-CCD IgE had strong reactivity to grass pollens. CONCLUSIONS AND CLINICAL IMPORTANCE A similar prevalence of anti-CCD IgE was found in healthy and atopic dogs. Further investigation is warranted to determine the clinical significance of anti-CCD IgE antibodies in dogs, how they are best detected and if blocking these antibodies during diagnostic testing has clinical value.
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Affiliation(s)
- Michelle L Piccione
- Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison, WI, 53706, USA
| | - Douglas J DeBoer
- Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison, WI, 53706, USA
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Abstract
α-Gal syndrome results from sensitization to the carbohydrate epitope galactose-α-1,3-galactose (α‑gal). The allergen occurs in mammalian meat and innards, but also in other foods and medical products of animal origin. Allergic reactions generally occur delayed after allergen intake with a latency period, depending on the individual tolerance threshold and the influence of cofactors. Details in the patient's medical history can help to establish the suspected diagnosis of α‑gal syndrome. Confirmation of the diagnosis requires the expertise of specialists, experienced with the implementation and interpretation of in vitro and in vivo diagnostic tests. Whereas skin prick testing with commercial whole-meat extracts often does not provide reliable results, allergen-specific IgE (α-gal) is generally detectable in affected patients. Cell-based tests such as the basophil activation test are currently only employed in an experimental setting. To evaluate, whether a sensitization is clinically relevant, an in-patient oral food challenge should be performed, using for example cooked pork or porcine kidney in addition to suspected cofactors.
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Callery EL, Keymer C, Barnes NA, Rowbottom AW. Component-resolved diagnostics in the clinical and laboratory investigation of allergy. Ann Clin Biochem 2019; 57:26-35. [PMID: 31480853 DOI: 10.1177/0004563219877434] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The diagnosis and management of allergy is complex; the clinical symptoms associated with allergic reactions span a broad spectrum of severity, from mild hay fever-type symptoms through to life-threatening anaphylaxis. Obtaining an allergy-focused clinical history is therefore vital for identifying possible allergic triggers and directing testing. However, this focus could be changing as scientific and technological advances have paved the way for developments within in vitro testing for allergy. With knowledge of allergens at the molecular level expanding, there are now the facilities to characterize the sensitization profiles of allergy sufferers and determine the specific molecules (or components) against which the allergen-inducing immunoglobulin type E proteins have been produced. This technology is termed component-resolved diagnostics. We know that accurate identification of immunoglobulin type E specificity, the source of the causative allergen, and knowledge of potential allergic cross-reactivities are required for optimal clinical management of allergy patients. These factors can make allergy a diagnostic challenge outside of a specialist centre, and contribute to the difficulties associated with requesting and interpreting allergy tests. The incorporation of component-resolved diagnostics into current practice has provided a platform for patient-tailored risk stratification and improved the application of allergen-specific immunotherapy, revolutionizing specialist management of these patients. This review discusses the roles of each type of testing in allergy management and predictions for future pathways.
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Affiliation(s)
- Emma L Callery
- Department of Immunology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK
| | - Catherine Keymer
- Department of Immunology, Royal Liverpool University Hospital, Liverpool, UK
| | - Nicholas A Barnes
- Faculty of Biology Medicine and Health, Manchester Academy for Healthcare Scientist Education, The University of Manchester, Manchester, UK
| | - Anthony W Rowbottom
- Department of Immunology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK.,School of Medicine, University of Central Lancashire, Preston, UK
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Sex difference in IgE sensitization associated with alcohol consumption in the general population. Sci Rep 2019; 9:12131. [PMID: 31431645 PMCID: PMC6702201 DOI: 10.1038/s41598-019-48305-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Accepted: 07/30/2019] [Indexed: 01/09/2023] Open
Abstract
The association of alcohol consumption and immunoglobulin E (IgE) sensitization is debated. Few population-based studies have investigated whether such associations differ by sex. We explored the association of alcohol consumption with IgE sensitization in the general population, stratified by sex. We analyzed data for 1,723 adults from the 2010 Korean National Health and Nutrition Examination Survey. We divided subjects into three groups according to their self-reported alcohol consumption or serum level of gamma-glutamyltransferase (GGT), an objective marker of alcohol consumption. After adjustments, the odds ratios (ORs) of male high-risk drinkers were 2.09 (95% confidence interval [CI], 1.34–3.28) for total IgE and 1.71 (95% CI, 1.03–2.83) for Dermatophagoides farinae (DF)-specific IgE compared with male low-risk drinkers. In females, the dog-specific IgE level was associated with high-risk drinking (OR, 11.74; 95% CI, 2.04–67.24). The ORs of males in the high-serum-GGT group were 2.73 (95% CI, 1.72–4.33) for total IgE and 2.17 (95% CI, 1.35–3.47) for DF-specific IgE compared with those in the low-serum-GGT group. This study suggests a possible link between alcohol consumption and IgE sensitization, moreover, the risk of IgE sensitization was significantly higher in male high-risk drinkers. Therefore, clinicians should consider the risk of IgE sensitization possibly afflicting male high-risk drinkers.
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