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Jappe U, Kolaly T, de Vries MS, Gülsen A, Homann A. Connecting Diagnostics and Clinical Relevance of the α-Gal Syndrome-Individual Sensitization Patterns of Patients with Suspected α-Gal-Associated Allergy. Nutrients 2025; 17:1541. [PMID: 40362849 DOI: 10.3390/nu17091541] [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] [Received: 03/27/2025] [Revised: 04/27/2025] [Accepted: 04/28/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND/OBJECTIVES Sensitization to the carbohydrate antigen α-Gal is associated with allergic reactions against different types of food that contain α-Gal (e.g., mammalian meat). This form of allergy is termed α-Gal syndrome (AGS), and the diagnosis is challenging due to delayed symptom onset and cross-reactivity with multiple mammalian products. It is estimated that AGS is underdiagnosed, pointing to an unmet need for patient care. METHODS Sera from patients with suspected AGS based on clinical history were analyzed by ImmunoCAP and the IgE cross-reactivity immune profiling (ICRIP) system specifically developed by us. IgE from patient sera against different forms of α-Gal was analyzed using α-Gal-containing analytes and negative controls. RESULTS Sera from 33 patients with suspected AGS were analyzed. Sera from 22 patients yielded a clearly positive signal (>0.35 kU/L) for IgE against α-Gal in ImmunoCAP. For 7 of the remaining 11 patients with negative or ambiguous (IgE level between 0.1 and 0.35 kU/L) results in ImmunoCAP, ICRIP analyses supported the suspected association of the allergy symptoms with IgE against α-Gal components. This component-resolved analysis helps the allergist to provide an individual diagnosis for each patient. CONCLUSIONS The diagnosis of AGS is challenging. An interplay between clinical history and lab analysis via ImmunoCAP and the specifically developed ICRIP system helps patients and allergists in establishing the correct diagnosis, thereby preventing accidental exposure and recurrent AGS episodes.
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Affiliation(s)
- Uta Jappe
- Division of Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 23845 Borstel, Germany
- Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, UKSH Campus Lübeck, University of Lübeck, 23538 Lübeck, Germany
| | - Tahmina Kolaly
- Division of Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 23845 Borstel, Germany
| | - Mareike S de Vries
- Division of Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 23845 Borstel, Germany
| | - Askin Gülsen
- Division of Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 23845 Borstel, Germany
- Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, UKSH Campus Lübeck, University of Lübeck, 23538 Lübeck, Germany
- Division of Cardiology, Pulmonary Diseases, Vascular Medicine, University Hospital Duesseldorf, 40225 Düsseldorf, Germany
| | - Arne Homann
- Division of Clinical and Molecular Allergology, Priority Research Area Chronic Lung Diseases, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 23845 Borstel, Germany
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Peterson CJ, Mohankumar P, Tarbox JA, Nugent K. Alpha-Gal Syndrome: A Review for the General Internist. Am J Med Sci 2025; 369:313-320. [PMID: 39615839 DOI: 10.1016/j.amjms.2024.11.015] [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] [Received: 06/27/2024] [Revised: 11/21/2024] [Accepted: 11/27/2024] [Indexed: 12/17/2024]
Abstract
Alpha-gal syndrome develops in some individuals who have had tick bites which result in IgE responses to alpha-gal, a carbohydrate not found in humans. Patients with alpha-gal syndrome develop symptoms when they ingest mammalian meat, which contains this oligosaccharide. Often the response to this exposure is delayed and occurs 2 to 6 h post-ingestion. Symptoms can include skin rashes, urticaria, gastrointestinal symptoms, and occasionally anaphylaxis. In some patients, the initial site of the skin reaction is at the location of the prior tick bite. The frequency of the syndrome is uncertain but the geographic distribution is predominantly in areas with the lone star tick. The diagnosis depends on careful attention to the time interval between the ingestion of meat and the development of the symptoms. In addition, a history of prior tick bites is important for considering this diagnosis. Diagnostic studies include skin tests, serologic tests for specific IgE, and food challenges, with varying risks for anaphylaxis. The treatment of patients with acute presentations frequently includes intramuscular epinephrine, oral antihistamines, and corticosteroids. Long-term management involves diet modification with the elimination of meat. Patients can also have adverse reactions to medications, such as set cetuximab, heparin, monoclonal antibodies, and pancreatic enzymes, and clinicians will likely have difficulty identifying these reactions. If patients have a good response to diet modification and have a significant reduction in their specific IgE level to alpha-gal, they potentially can resume eating meat in their diet. This should be done under the direction of a specialist.
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Affiliation(s)
- Christopher J Peterson
- Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA.
| | - Poornachandran Mohankumar
- Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - James A Tarbox
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
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3
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McCladdie T, Herman M. Alpha-Gal Syndrome: An Emerging Tick-Borne Allergy to Red Meat. Cureus 2025; 17:e79746. [PMID: 40161126 PMCID: PMC11954431 DOI: 10.7759/cureus.79746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/26/2025] [Indexed: 04/02/2025] Open
Abstract
Alpha-gal syndrome (AGS) is a delayed-onset food allergy triggered by an immune response to galactose-α-1,3-galactose (alpha-gal), a carbohydrate associated with Lone Star tick bites. A 45-year-old female presented with a 9-month history of nausea and abdominal pain consistently associated with red meat consumption. Initial workup, including routine labs, imaging, and endoscopy, was unremarkable, but specific IgE testing confirmed AGS. Management included strict avoidance of red meat, carrying an epinephrine auto-injector, and referral to an allergist for education and long-term care. This case highlights the diagnostic challenges posed by the delayed reaction and the importance of dietary vigilance and emergency preparedness. Increased awareness of AGS is essential, especially in regions where tick exposure is prevalent.
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Affiliation(s)
- Tyanna McCladdie
- Osteopathic Medicine, Philadelphia College of Osteopathic Medicine, Moultrie, USA
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Propst SBH, Thompson DK. Alpha-gal syndrome and the gastrointestinal reaction: a narrative review. FRONTIERS IN ALLERGY 2025; 6:1535103. [PMID: 39927113 PMCID: PMC11802538 DOI: 10.3389/falgy.2025.1535103] [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: 11/26/2024] [Accepted: 01/10/2025] [Indexed: 02/11/2025] Open
Abstract
Gastrointestinal (GI) disturbances such as abdominal pain, nausea, and diarrhea are infrequently attributed to food allergies as an initial diagnosis in the absence of more traditional allergic reactions like hives, angioedema, or anaphylaxis. Alpha-gal syndrome (AGS) is an atypical and under-recognized allergy characterized by a delayed hypersensitivity reaction to the oligosaccharide galactose-α-1,3-galactose, a carbohydrate found in non-primate mammalian meat and derived products. This review of the current literature on AGS focuses on GI manifestations and diagnostic challenges. While clinical presentations of AGS vary widely, predominant or isolated GI symptoms, when manifested, can overlap with other disorders, thus making a timely and accurate diagnosis challenging. Here we provide an updated review of the epidemiology, pathophysiology, clinical presentation, and management of AGS. Current diagnostic approaches, treatment strategies, and areas requiring further research are also discussed.
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Affiliation(s)
- Susan B. H. Propst
- School of Pharmacy, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC, United States
| | - Dorothea K. Thompson
- Department of Pharmaceutical and Clinical Sciences, College of Pharmacy & Health Sciences, Campbell University, Buies Creek, NC, United States
- Department of Pharmaceutical Sciences, School of Pharmacy, South College, Knoxville, TN, United States
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5
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Sharma SR, Hussain S, Choudhary SK, Commins SP, Karim S. Identification of Alpha-Gal glycolipids in saliva of Lone-Star Tick (Amblyomma americanum). Ticks Tick Borne Dis 2024; 15:102384. [PMID: 39053323 DOI: 10.1016/j.ttbdis.2024.102384] [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] [Received: 02/21/2024] [Revised: 07/11/2024] [Accepted: 07/18/2024] [Indexed: 07/27/2024]
Abstract
Alpha-Gal Syndrome (AGS) is a delayed allergic reaction triggered by IgE antibodies targeting galactose-α-1,3-galactose (α-gal), prevalent in red meat. Its global significance has increased, with over 450,000 estimated cases in the United States alone. AGS is linked to tick bites, causing sensitization and elevated α-gal specific IgE levels. However, the precise mechanisms and tick intrinsic factors contributing to AGS development post-tick bites remain unclear. This study aims to characterize the alpha-gal conjugated lipid antigens in Amblyomma americanum (Am. americanum) salivary glands and saliva. Nanospray ionization mass spectrometry (NSI-MS) analysis revealed the identification of α-gal bound lipid antigens in Am. americanum saliva. Additionally, the activation of basophils by extracted alpha-gal bound lipids and proteins provides evidence of their antigenic capabilities.
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Affiliation(s)
- Surendra Raj Sharma
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
| | - Sabir Hussain
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China
| | - Shailesh K Choudhary
- Department of Medicine & Pediatrics, Division of Allergy & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Scott P Commins
- Department of Medicine & Pediatrics, Division of Allergy & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Shahid Karim
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA.
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Peterson L, Yacoub MH, Ayares D, Yamada K, Eisenson D, Griffith BP, Mohiuddin MM, Eyestone W, Venter JC, Smolenski RT, Rothblatt M. Physiological basis for xenotransplantation from genetically modified pigs to humans. Physiol Rev 2024; 104:1409-1459. [PMID: 38517040 PMCID: PMC11390123 DOI: 10.1152/physrev.00041.2023] [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] [Received: 10/26/2023] [Revised: 03/06/2024] [Accepted: 03/14/2024] [Indexed: 03/23/2024] Open
Abstract
The collective efforts of scientists over multiple decades have led to advancements in molecular and cellular biology-based technologies including genetic engineering and animal cloning that are now being harnessed to enhance the suitability of pig organs for xenotransplantation into humans. Using organs sourced from pigs with multiple gene deletions and human transgene insertions, investigators have overcome formidable immunological and physiological barriers in pig-to-nonhuman primate (NHP) xenotransplantation and achieved prolonged pig xenograft survival. These studies informed the design of Revivicor's (Revivicor Inc, Blacksburg, VA) genetically engineered pigs with 10 genetic modifications (10 GE) (including the inactivation of 4 endogenous porcine genes and insertion of 6 human transgenes), whose hearts and kidneys have now been studied in preclinical human xenotransplantation models with brain-dead recipients. Additionally, the first two clinical cases of pig-to-human heart xenotransplantation were recently performed with hearts from this 10 GE pig at the University of Maryland. Although this review focuses on xenotransplantation of hearts and kidneys, multiple organs, tissues, and cell types from genetically engineered pigs will provide much-needed therapeutic interventions in the future.
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Affiliation(s)
- Leigh Peterson
- United Therapeutics Corporation, Silver Spring, Maryland, United States
| | | | - David Ayares
- United Therapeutics Corporation, Silver Spring, Maryland, United States
| | - Kazuhiko Yamada
- Department of Surgery, Division of Transplantation, Johns Hopkins Medicine, Baltimore, Maryland, United States
| | - Daniel Eisenson
- Department of Surgery, Division of Transplantation, Johns Hopkins Medicine, Baltimore, Maryland, United States
| | - Bartley P Griffith
- University of Maryland Medical Center, Baltimore, Maryland, United States
| | | | - Willard Eyestone
- United Therapeutics Corporation, Silver Spring, Maryland, United States
| | - J Craig Venter
- J. Craig Venter Institute, Rockville, Maryland, United States
| | | | - Martine Rothblatt
- United Therapeutics Corporation, Silver Spring, Maryland, United States
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Reshetnyak YK, Andreev OA, Engelman DM. Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides. Front Pharmacol 2024; 15:1355893. [PMID: 38545547 PMCID: PMC10965573 DOI: 10.3389/fphar.2024.1355893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 01/05/2024] [Indexed: 11/11/2024] Open
Abstract
The family of pH (Low) Insertion Peptides (pHLIP) comprises a tumor-agnostic technology that uses the low pH (or high acidity) at the surfaces of cells within the tumor microenvironment (TME) as a targeted biomarker. pHLIPs can be used for extracellular and intracellular delivery of a variety of imaging and therapeutic payloads. Unlike therapeutic delivery targeted to specific receptors on the surfaces of particular cells, pHLIP targets cancer, stromal and some immune cells all at once. Since the TME exhibits complex cellular crosstalk interactions, simultaneous targeting and delivery to different cell types leads to a significant synergistic effect for many agents. pHLIPs can also be positioned on the surfaces of various nanoparticles (NPs) for the targeted intracellular delivery of encapsulated payloads. The pHLIP technology is currently advancing in pre-clinical and clinical applications for tumor imaging and treatment.
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Affiliation(s)
- Yana K. Reshetnyak
- Physics Department, University of Rhode Island, Kingston, RI, United States
| | - Oleg A. Andreev
- Physics Department, University of Rhode Island, Kingston, RI, United States
| | - Donald M. Engelman
- Molecular Biophysics and Biochemistry Department, Yale, New Haven, CT, United States
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8
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Saadalla A, Jacela J, Poll R, Slev P. Immunoassay Testing of Alpha-Gal Specific Immunoglobulin-E: Data from a National Reference Laboratory. J Appl Lab Med 2024; 9:262-272. [PMID: 38424720 DOI: 10.1093/jalm/jfad115] [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: 07/30/2023] [Accepted: 10/24/2023] [Indexed: 03/02/2024]
Abstract
BACKGROUND Immunoassay measurements of serum alpha-gal (AG) specific IgE (sIgE) enable antibody detection and quantification with high sensitivity and specificity and are essential for AG syndrome diagnosis and patient management. We here present and analyze results from over 15 000 patient serum samples tested using the ImmunoCAP (Thermo/Phadia) assay. METHODS AG-sIgE levels and positivity rates were correlated to patient age, gender, geographic location, repeat testing results, sIgE levels to co-tested red meat whole allergen extracts, and Rocky Mountain spotted fever (RMSF) serology performed on a subset of patient samples. RESULTS Of the tested samples, 36.7% contained detectable (>0.1 KUA/L) AG-sIgE. Antibody levels were higher in patients of older age, in samples submitted from lower midwestern and southern states, and during the June-December period of the year. Specific IgE to co-tested red meat whole allergens showed moderate to strong correlation to AG-sIgE and were of lower levels. Samples with positive RMSF IgG titers (≥1:64) were of overall higher AG-IgE levels. CONCLUSION Findings are consistent with the role of lone star ticks in AG syndrome pathogenesis. Levels of measured sIgE to AG are higher than co-tested sIgE to red meat whole allergen, consistent with the improved diagnostic performance of component-resolved testing.
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Affiliation(s)
- Abdulrahman Saadalla
- Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, United States
- Immunology section, ARUP Laboratories, Salt Lake City, UT, United States
| | - Jessica Jacela
- Immunology section, ARUP Laboratories, Salt Lake City, UT, United States
| | - Rick Poll
- Immunology section, ARUP Laboratories, Salt Lake City, UT, United States
| | - Patricia Slev
- Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, United States
- Immunology section, ARUP Laboratories, Salt Lake City, UT, United States
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Peterson H, Wells DA, Marjoncu D, Holman K. Use of antithymocyte globulin (rabbit) in a patient with known alpha-gal syndrome undergoing allogenic stem cell transplantation. J Oncol Pharm Pract 2024; 30:417-421. [PMID: 37936368 DOI: 10.1177/10781552231212648] [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] [Indexed: 11/09/2023]
Abstract
INTRODUCTION Alpha-gal syndrome (AGS) is a hypersensitivity disorder in which tick bites-most commonly from the lone star tick (Ambylomma americanum)-trigger immunoglobulin E-mediated hypersensitivity reaction upon exposure to oligosaccharide galactosse-alpha-1,3-galactose (α-gal). α-gal is most notorious for being found in "red meat" products but is present in mammalian meats such as beef, pork, lamb, rabbit, and others. Manifestations of AGS hypersensitivity are variable. There is currently no in vivo data describing allergic reactions against rabbit products in patients with AGS. CASE REPORT Here, we describe a case of a 44-year-old male with myelodysplastic syndrome and a known history of AGS undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) with the use of rabbit antithymocyte globulin (rATG) for graft-versus-host disease (GVHD) prophylaxis. MANAGEMENT AND OUTCOME The risk of cross-reactivity against rATG in our patient with AGS could not be ruled out and, therefore, a test dose was administered. The patient tolerated the test dose with no signs of anaphylaxis. After demonstrating tolerance to the test dose, rATG was utilized for GVHD prophylaxis. DISCUSSION Due to the heterogeneity of AGS manifestations in patients, the use of rATG in patients with known AGS should be considered on a case-by-case basis. The administration of a test dose may help predict the occurrence of severe hypersensitivity reactions. The limited data surrounding the risk of AGS with rabbit-containing products and the various indications for the use of rATG warrants more in-depth study of the reactivity of this medication in this population.
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Affiliation(s)
- Hannah Peterson
- Department of Pharmacy, Methodist Le Bonheur Healthcare - University Hospital, Memphis, TN, USA
| | - Drew A Wells
- Department of Pharmacy, Methodist Le Bonheur Healthcare - University Hospital, Memphis, TN, USA
- Department of Clinical Pharmacy and Translational Science, The University of Tennessee Health Science Center College of Pharmacy, Memphis, TN, USA
| | - Dennis Marjoncu
- Department of Pharmacy, Methodist Le Bonheur Healthcare - University Hospital, Memphis, TN, USA
| | - Kori Holman
- Department of Pharmacy, Methodist Le Bonheur Healthcare - University Hospital, Memphis, TN, USA
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Sharma SR, Choudhary SK, Vorobiov J, Commins SP, Karim S. Tick bite-induced alpha-gal syndrome and immunologic responses in an alpha-gal deficient murine model. Front Immunol 2024; 14:1336883. [PMID: 38390396 PMCID: PMC10882631 DOI: 10.3389/fimmu.2023.1336883] [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: 11/11/2023] [Accepted: 12/26/2023] [Indexed: 02/24/2024] Open
Abstract
Introduction Alpha-Gal Syndrome (AGS) is a delayed allergic reaction due to specific IgE antibodies targeting galactose-α-1,3-galactose (α-gal), a carbohydrate found in red meat. This condition has gained significant attention globally due to its increasing prevalence, with more than 450,000 cases estimated just in the United States alone. Previous research has established a connection between AGS and tick bites, which sensitize individuals to α-gal antigens and elevate the levels of specific IgE. However, the precise mechanism by which tick bites influence the host's immune system and contribute to the development of AGS remains poorly understood. This study investigates various factors related to ticks and the host associated with the development of AGS following a tick bite, using mice with a targeted disruption of alpha-1,3-galactosyltransferase (AGKO) as a model organism. Methods Lone-star tick (Amblyomma americanum) and gulf-coast tick (Amblyomma maculatum) nymphs were used to sensitize AGKO mice, followed by pork meat challenge. Tick bite site biopsies from sensitized and non-sensitized mice were subjected to mRNA gene expression analysis to assess the host immune response. Antibody responses in sensitized mice were also determined. Results Our results showed a significant increase in the total IgE, IgG1, and α-gal IgG1 antibodies titers in the lone-star tick-sensitized AGKO mice compared to the gulf-coast tick-sensitized mice. Pork challenge in Am. americanum -sensitized mice led to a decline in body temperature after the meat challenge. Gene expression analysis revealed that Am. americanum bites direct mouse immunity toward Th2 and facilitate host sensitization to the α-gal antigen. Conclusion This study supports the hypothesis that specific tick species may increase the risk of developing α-gal-specific IgE and hypersensitivity reactions or AGS, thereby providing opportunities for future research on the mechanistic role of tick and host-related factors in AGS development.
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Affiliation(s)
- Surendra Raj Sharma
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
| | - Shailesh K. Choudhary
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | - Julia Vorobiov
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | - Scott P. Commins
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | - Shahid Karim
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
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Karim S, Leyva-Castillo JM, Narasimhan S. Tick salivary glycans - a sugar-coated tick bite. Trends Parasitol 2023; 39:1100-1113. [PMID: 37838514 DOI: 10.1016/j.pt.2023.09.012] [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: 07/21/2023] [Revised: 09/22/2023] [Accepted: 09/22/2023] [Indexed: 10/16/2023]
Abstract
Ticks are hematophagous arthropods that transmit disease-causing pathogens worldwide. Tick saliva deposited into the tick-bite site is composed of an array of immunomodulatory proteins that ensure successful feeding and pathogen transmission. These salivary proteins are often glycosylated, and glycosylation is potentially critical for the function of these proteins. Some salivary glycans are linked to the phenomenon of red meat allergy - an allergic response to red meat consumption in humans exposed to certain tick species. Tick salivary glycans are also invoked in the phenomenon of acquired tick resistance wherein non-natural host species exposed to tick bites develop an immune response that thwarts subsequent tick feeding. This review dwells on our current knowledge of these two phenomena, thematically linked by salivary glycans.
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Affiliation(s)
- Shahid Karim
- University of Southern Mississippi, Hattiesburg, MS, USA
| | - Juan Manuel Leyva-Castillo
- Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Sukanya Narasimhan
- Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven-06520, CT, USA.
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12
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Sharma SR, Choudhary SK, Vorobiov J, Commins SP, Karim S. Tick bite-induced Alpha-Gal Syndrome and Immunologic Responses in an Alpha-Gal Deficient Murine Model. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.11.09.566281. [PMID: 38014105 PMCID: PMC10680608 DOI: 10.1101/2023.11.09.566281] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2023]
Abstract
Introduction Alpha-Gal Syndrome (AGS) is a delayed allergic reaction due to specific IgE antibodies targeting galactose-α-1,3-galactose (α-gal), a carbohydrate found in red meat. This condition has gained significant attention globally due to its increasing prevalence, with more than 450,000 cases estimated in the United States alone. Previous research has established a connection between AGS and tick bites, which sensitize individuals to α-gal antigens and elevate the levels of α-gal specific IgE. However, the precise mechanism by which tick bites influence the hosťs immune system and contribute to the development of AGS remains poorly understood. This study investigates various factors related to ticks and the host associated with the development of AGS following a tick bite, using mice with a targeted disruption of alpha-1,3-galactosyltransferase (AGKO) as a model organism. Methods Lone-star tick (Amblyomma americanum) and gulf-coast tick (Amblyomma maculatum) nymphs were used to sensitize AGKO mice, followed by pork meat challenge. Tick bite site biopsies from sensitized and non-sensitized mice were subjected to mRNA gene expression analysis to assess the host immune response. Antibody responses in sensitized mice were also determined. Results Our results showed a significant increase in the titer of total IgE, IgG1, and α-gal IgG1 antibodies in the lone-star tick-sensitized AGKO mice compared to the gulf-coast tick-sensitized mice. Pork challenge in Am. americanum -sensitized mice led to a decline in body temperature after the meat challenge. Gene expression analysis revealed that Am. americanum bites direct mouse immunity toward Th2 and facilitate host sensitization to the α-gal antigen, while Am. maculatum did not. Conclusion This study supports the hypothesis that specific tick species may increase the risk of developing α-gal-specific IgE and hypersensitivity reactions or AGS, thereby providing opportunities for future research on the mechanistic role of tick and host-related factors in AGS development.
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Affiliation(s)
- Surendra Raj Sharma
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
| | - Shailesh K Choudhary
- Department of Medicine & Pediatrics, University of North Carolina, Chapel Hill, NC 27599-7280, USA
| | - Julia Vorobiov
- Department of Medicine & Pediatrics, University of North Carolina, Chapel Hill, NC 27599-7280, USA
| | - Scott P Commins
- Department of Medicine & Pediatrics, University of North Carolina, Chapel Hill, NC 27599-7280, USA
| | - Shahid Karim
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
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Glynn D, Halma J, Welch H, Shakhnovich V, Friesen C. Nonanaphylactic Variant of Alpha-Gal Syndrome as an Etiology for Chronic Gastrointestinal Symptoms in Children. J Pediatr 2023; 259:113486. [PMID: 37201681 DOI: 10.1016/j.jpeds.2023.113486] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 04/27/2023] [Accepted: 05/08/2023] [Indexed: 05/20/2023]
Abstract
We report 3 pediatric patients who presented with only nonanaphylactic symptoms of alpha-gal syndrome. This report highlights the necessity of not discounting alpha-gal syndrome from a differential diagnosis for patients with recurrent gastrointestinal distress and emesis after consuming mammalian meat, even in the absence of an anaphylactic reaction.
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Affiliation(s)
- De'mond Glynn
- University of Kansas School of Medicine, Kansas City, MO
| | - Jennifer Halma
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Kansas City, Kansas City, MO
| | - Hannah Welch
- Nutrition Department, Children's Mercy Kansas City, Kansas City, MO
| | - Valentina Shakhnovich
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Kansas City, Kansas City, MO; Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO
| | - Craig Friesen
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Kansas City, Kansas City, MO; Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO.
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Coumes-Salomon C, Géniaux H, Boumedienne A, Touraine F, Vincent F, Bellet-Fraysse E. Les tests cutanés aux héparines chez les patients sensibilisés à l’alpha-gal au CHU de Limoges. REVUE FRANÇAISE D'ALLERGOLOGIE 2023. [DOI: 10.1016/j.reval.2023.103323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/27/2023]
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15
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Lee CJ, McGill SK. Food Allergies and Alpha-gal Syndrome for the Gastroenterologist. Curr Gastroenterol Rep 2023; 25:21-30. [PMID: 36705797 DOI: 10.1007/s11894-022-00860-7] [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: 12/02/2022] [Indexed: 01/28/2023]
Abstract
PURPOSE OF REVIEW Food allergies are typically not considered as a cause of gastrointestinal (GI) distress without additional allergic symptoms, apart from celiac disease and eosinophilic esophagitis. However, recent reports of patients with alpha-gal syndrome who presented with GI-only symptoms like abdominal pain, vomiting, and diarrhea challenge this paradigm. Alpha-gal syndrome is an IgE-mediated allergy characterized by delayed reactions after eating mammalian meat or mammalian-derived products that contain galactose-alpha-1,3-galactose (alpha-gal). The purpose of this review is to discuss our current understanding of food allergies, GI illness, and the GI manifestations of alpha-gal syndrome. RECENT FINDINGS Among Southeastern U.S. GI clinic patients who screened positive for serum alpha-gal IgE, a majority of patients reported significant symptom improvement on an alpha-gal-avoidant diet, suggesting that the allergy had played a role in their GI symptoms. Diagnosis of alpha-gal syndrome is typically made with concerning allergic symptoms, elevated alpha-gal specific IgE in the serum, and symptom improvement on an alpha-gal avoidant diet. Alpha-gal syndrome can cause a delayed allergic response that is increasingly recognized worldwide, including among patients with predominant GI symptoms.
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Affiliation(s)
- Christopher J Lee
- Department of Internal Medicine, University of North Carolina at Chapel Hill, 130 Mason Farm Road, Chapel Hill, NC, 27514, USA
| | - Sarah K McGill
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of North Carolina at Chapel Hill, 130 Mason Farm Road, Chapel Hill, NC, 27514, USA.
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16
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Serrier J, Davy JB, Dupont B, Clarisse B, Parienti JJ, Petit G, Khoy K, Ollivier Y, Gervais R, Mariotte D, Le Mauff B. Validation of an anti-α-Gal IgE fluoroenzyme-immunoassay for the screening of patients at risk of severe anaphylaxis to cetuximab. BMC Cancer 2023; 23:32. [PMID: 36624467 PMCID: PMC9827640 DOI: 10.1186/s12885-023-10501-5] [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: 11/02/2022] [Accepted: 01/02/2023] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND The link between immediate hypersensitivity reactions (HSR) following the first cetuximab infusion and the IgE sensitization against anti-galactose-α-1,3-galactose (α-Gal) is now well-established. An automated Fluoroenzyme-Immunoassay (FEIA) is available and may facilitate the screening of patients with anti-α-Gal IgE before treatment. METHODS This study aimed to evaluate its performances as compared to a previously validated anti-cetuximab IgE ELISA, using 185 samples from two previously studied cohorts. RESULTS Despite 21.1% of discrepancies between the two techniques, FEIA discriminated better positive patients and similarly negative ones with a ≥ 0.525 kUA/L threshold. Sensitivity was 87.5% for both tests, specificity was better for FEIA (96.3% vs ELISA: 82.1%). FEIA had a higher positive likelihood ratio (23.9 vs ELISA: 4.89) and a similar negative likelihood ratio (0.13 vs ELISA: 0.15). In our population, the risk of severe HSR following a positive test was higher with FEIA (56.7% vs ELISA: 19.6%) and similar following a negative test (0.7% vs ELISA: 0.8%). CONCLUSION Although the predictive value of the IgE screening before cetuximab infusion remains discussed, this automated commercial test can identify high-risk patients and is suitable for routine use in laboratories. It could help avoiding cetuximab-induced HSR by a systematic anti-α-Gal IgE screening before treatment.
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Affiliation(s)
- Julien Serrier
- grid.411149.80000 0004 0472 0160Department of Immunology and Histocompatibility, CHU Caen, Caen, France ,grid.412043.00000 0001 2186 4076University of Caen Normandy, Caen, France ,INSERM U1237, Physiopathology and Imaging of Neurological Disorders, Caen, France
| | - Jean-Baptiste Davy
- grid.411149.80000 0004 0472 0160Department of Immunology and Histocompatibility, CHU Caen, Caen, France
| | - Benoît Dupont
- grid.411149.80000 0004 0472 0160Department of Hepato-Gastroenterology and Nutrition, CHU Caen, Caen, France
| | - Bénédicte Clarisse
- grid.418189.d0000 0001 2175 1768Clinical Research Department, Centre François Baclesse, Caen, France
| | - Jean-Jacques Parienti
- grid.412043.00000 0001 2186 4076University of Caen Normandy, Caen, France ,grid.411149.80000 0004 0472 0160Department of Clinical Research and Biostatistics, CHU Caen, Caen, France
| | - Gautier Petit
- grid.411149.80000 0004 0472 0160Department of Immunology and Histocompatibility, CHU Caen, Caen, France
| | - Kathy Khoy
- grid.411149.80000 0004 0472 0160Department of Immunology and Histocompatibility, CHU Caen, Caen, France
| | - Yann Ollivier
- grid.411149.80000 0004 0472 0160 University Center for Allergic Diseases (CUMA), CHU Caen, Caen, France
| | - Radj Gervais
- grid.418189.d0000 0001 2175 1768Medical Oncology Department, Centre François Baclesse, Caen, France
| | - Delphine Mariotte
- grid.411149.80000 0004 0472 0160Department of Immunology and Histocompatibility, CHU Caen, Caen, France
| | - Brigitte Le Mauff
- grid.411149.80000 0004 0472 0160Department of Immunology and Histocompatibility, CHU Caen, Caen, France ,grid.412043.00000 0001 2186 4076University of Caen Normandy, Caen, France ,INSERM U1237, Physiopathology and Imaging of Neurological Disorders, Caen, France
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17
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DuPont M, Visca H, Moshnikova A, Engelman DM, Reshetnyak YK, Andreev OA. Tumor treatment by pHLIP-targeted antigen delivery. Front Bioeng Biotechnol 2023; 10:1082290. [PMID: 36686229 PMCID: PMC9853002 DOI: 10.3389/fbioe.2022.1082290] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 12/12/2022] [Indexed: 01/09/2023] Open
Abstract
Targeted antigen delivery allows activation of the immune system to kill cancer cells. Here we report the targeted delivery of various epitopes, including a peptide, a small molecule, and a sugar, to tumors by pH Low Insertion Peptides (pHLIPs), which respond to surface acidity and insert to span the membranes of metabolically activated cancer and immune cells within tumors. Epitopes linked to the extracellular ends of pH Low Insertion Peptide peptides were positioned at the surfaces of tumor cells and were recognized by corresponding anti-epitope antibodies. Special attention was devoted to the targeted delivery of the nine residue HA peptide epitope from the Flu virus hemagglutinin. The HA sequence is not present in the human genome, and immunity is readily developed during viral infection or immunization with KLH-HA supplemented with adjuvants. We tested and refined a series of double-headed HA-pHLIP agents, where two HA epitopes were linked to a single pH Low Insertion Peptide peptide via two Peg12 or Peg24 polymers, which enable HA epitopes to engage both antibody binding sites. HA-epitopes positioned at the surfaces of tumor cells remain exposed to the extracellular space for 24-48 h and are then internalized. Different vaccination schemes and various adjuvants, including analogs of FDA approved adjuvants, were tested in mice and resulted in a high titer of anti-HA antibodies. Anti-HA antibody binds HA-pHLIP in blood and travels as a complex leading to significant tumor targeting with no accumulation in organs and to hepatic clearance. HA-pHLIP agents induced regression of 4T1 triple negative breast tumor and B16F10 MHC-I negative melanoma tumors in immunized mice. The therapeutic efficacy potentially is limited by the drop of the level of anti-HA antibodies in the blood to background level after three injections of HA-pHLIP. We hypothesize that additional boosts would be required to keep a high titer of anti-HA antibodies to enhance efficacy. pH Low Insertion Peptide-targeted antigen therapy may provide an opportunity to treat tumors unresponsive to T cell based therapies, having a small number of neo-antigens, or deficient in MHC-I presentation at the surfaces of cancer cells either alone or in combination with other approaches.
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Affiliation(s)
- Michael DuPont
- Physics Department, University of Rhode Island, Kingston, RI, United States
| | - Hannah Visca
- Physics Department, University of Rhode Island, Kingston, RI, United States
| | - Anna Moshnikova
- Physics Department, University of Rhode Island, Kingston, RI, United States
| | - Donald M. Engelman
- Department of Molecular Biophysics and Biochemistry, Yale, New Haven, CT, United States
| | - Yana K. Reshetnyak
- Physics Department, University of Rhode Island, Kingston, RI, United States
| | - Oleg A. Andreev
- Physics Department, University of Rhode Island, Kingston, RI, United States
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18
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Poziomkowska-Gęsicka I. Idiopathic Anaphylaxis? Analysis of Data from the Anaphylaxis Registry for West Pomerania Province, Poland. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:16716. [PMID: 36554595 PMCID: PMC9779638 DOI: 10.3390/ijerph192416716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/05/2022] [Accepted: 12/07/2022] [Indexed: 06/17/2023]
Abstract
The most common causes of anaphylaxis, according to various authors and depending on the age of the studied groups, are: Hymenoptera venom, food, and medications. Unfortunately, we are not always able to indicate the cause of anaphylaxis. There are data in the literature where as many as 41% of all cases are idiopathic anaphylaxis. Since the introduction of new diagnostic methods such as molecular diagnostics (MD) in our centre, the percentage of idiopathic anaphylaxis in the Anaphylaxis Register has significantly decreased. The purpose of this study was to identify possible causes of idiopathic anaphylaxis in patients with a history of moderate to severe anaphylactic reactions. After using MD, the causative agent was found in another 29 people. The proportion of people with idiopathic anaphylaxis in the Registry decreased from 9.2% to 3.5%. There were no significant differences in the incidence, although men appear to be slightly more common in primary idiopathic anaphylaxis. The mean age of primary idiopathic anaphylaxis was 40 years, but this was as high as 51 for anaphylaxis with alpha-gal allergy. Exercise may or may not be present as a cofactor despite its established role, e.g., in wheat-dependent exercise-induced anaphylaxis (WDEIA). In most of the analyzed cases, i.e., 70%, the reaction took place within an hour. The longest time interval from exposure to the development of symptoms is in the case of alpha-gal allergy; in this analysis, it was at least 5 h after ingestion of the so-called "red meat". Patients are not aware of the disease, or further attacks cannot be prevented. As many as 80% had idiopathic anaphylaxis prior to visiting the centre, and 80% developed anaphylaxis after visiting the centre, which emphasizes the need to not stop the medical team in their search for the causes. As many as 93% of cases required medical intervention, of which adrenaline was used only in 34.5%, antihistamines in 86%, systemic glucocorticosteroids (sCS) in 75%, and fluids in 62% of cases. A total of 83% of patients received an emergency kit for self-administration. Idiopathic anaphylaxis can be resolved as known-cause anaphylaxis after a thorough medical history and, if possible, without exposing the patient after using appropriate, modern in vitro diagnostic methods, including molecular diagnostics. The diagnosis of idiopathic anaphylaxis should extend the diagnosis to include alpha-gal syndrome, LTP syndrome and WDEIA.
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Affiliation(s)
- Iwona Poziomkowska-Gęsicka
- Clinical Allergology Department, Pomeranian Medical University (PMU) in Szczecin, 70-111 Szczecin, Poland
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19
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Khan DA, Banerji A, Blumenthal KG, Phillips EJ, Solensky R, White AA, Bernstein JA, Chu DK, Ellis AK, Golden DBK, Greenhawt MJ, Horner CC, Ledford D, Lieberman JA, Oppenheimer J, Rank MA, Shaker MS, Stukus DR, Wallace D, Wang J, Khan DA, Golden DBK, Shaker M, Stukus DR, Khan DA, Banerji A, Blumenthal KG, Phillips EJ, Solensky R, White AA, Bernstein JA, Chu DK, Ellis AK, Golden DBK, Greenhawt MJ, Horner CC, Ledford D, Lieberman JA, Oppenheimer J, Rank MA, Shaker MS, Stukus DR, Wallace D, Wang J. Drug allergy: A 2022 practice parameter update. J Allergy Clin Immunol 2022; 150:1333-1393. [PMID: 36122788 DOI: 10.1016/j.jaci.2022.08.028] [Citation(s) in RCA: 233] [Impact Index Per Article: 77.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 08/18/2022] [Accepted: 08/30/2022] [Indexed: 12/14/2022]
Affiliation(s)
- David A Khan
- Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, Tex
| | - Aleena Banerji
- Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Kimberly G Blumenthal
- Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Elizabeth J Phillips
- Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn
| | - Roland Solensky
- Corvallis Clinic, Oregon State University/Oregon Health Science University College of Pharmacy, Corvallis, Ore
| | - Andrew A White
- Department of Allergy, Asthma and Immunology, Scripps Clinic, San Diego, Calif
| | - Jonathan A Bernstein
- Department of Internal Medicine, Division of Immunology, Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Derek K Chu
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada; The Research Institute of St Joe's Hamilton, Hamilton, Ontario, Canada
| | - Anne K Ellis
- Division of Allergy and Immunology, Department of Medicine, Queen's University, Kingston, Ontario, Canada
| | - David B K Golden
- Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md
| | - Matthew J Greenhawt
- Food Challenge and Research Unit Section of Allergy and Immunology, Children's Hospital Colorado University of Colorado School of Medicine, Aurora, Colo
| | - Caroline C Horner
- Department of Pediatrics, Division of Allergy Pulmonary Medicine, Washington University School of Medicine, St Louis, Mo
| | - Dennis Ledford
- Division of Allergy and Immunology, Department of Medicine, University of South Florida Morsani College of Medicine, Tampa, Fla; James A. Haley Veterans Affairs Hospital, Tampa, Fla
| | - Jay A Lieberman
- Division of Allergy and Immunology, The University of Tennessee Health Science Center, Memphis, Tenn
| | - John Oppenheimer
- Division of Allergy, Rutgers New Jersey Medical School, Rutgers, NJ
| | - Matthew A Rank
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic in Arizona, Scottsdale, Ariz
| | - Marcus S Shaker
- Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - David R Stukus
- Division of Allergy and Immunology, Nationwide Children's Hospital, Columbus, Ohio; The Ohio State University College of Medicine, Columbus, Ohio
| | - Dana Wallace
- Nova Southeastern Allopathic Medical School, Fort Lauderdale, Fla
| | - Julie Wang
- Division of Allergy and Immunology, Department of Pediatrics, The Elliot and Roslyn Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY
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20
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Narlesky MR, Palting A, Sukpraprut-Braaten S, Powell A, Strayhan R. Initiating Psychotropic Treatment in a Patient With Alpha-Gal Syndrome. Cureus 2022; 14:e28443. [PMID: 36176862 PMCID: PMC9512307 DOI: 10.7759/cureus.28443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2022] [Indexed: 11/12/2022] Open
Abstract
Alpha-gal syndrome, which is typically acquired by a tick bite, is an IgE-mediated immune response to galactose-alpha-1,3-galactose (alpha-gal), an oligosaccharide in most mammalian tissue. This report describes a 29-year-old Caucasian female with comorbid alpha-gal syndrome who presented to the inpatient psychiatric unit after an intentional overdose. Because of the patient’s alpha-gal syndrome, the treatment team worked with the hospital pharmacy to evaluate treatment options that did not contain mammalian products. After carefully reviewing the ingredients of suitable medications on formulary, the patient was started on a generic sertraline formulation that was free of mammalian derivatives. At the time of discharge, the patient reported significant symptom improvement and was free of symptoms suggesting an alpha-gal allergic reaction. This case illustrates the challenges of starting psychiatric medications in a patient with comorbid alpha-gal syndrome.
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21
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Suddenly Steakless: A Gastroenterologist's Guide to Managing Alpha-Gal Allergy. Am J Gastroenterol 2022; 117:822-826. [PMID: 35404302 DOI: 10.14309/ajg.0000000000001765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 04/04/2022] [Indexed: 12/11/2022]
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22
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Olivera-Ardid S, Bello-Gil D, Tuzikov A, Araujo RN, Ferrero-Alves Y, García Figueroa BE, Labrador-Horrillo M, García-Pérez AL, Bovin N, Mañez R. Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases. Front Immunol 2022; 13:873019. [PMID: 35432370 PMCID: PMC9009260 DOI: 10.3389/fimmu.2022.873019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 03/02/2022] [Indexed: 11/25/2022] Open
Abstract
Anti-αGal IgE antibodies mediate a spreading allergic condition known as αGal-syndrome (AGS). People exposed to hard tick bites are sensitized to αGal, producing elevated levels of anti-αGal IgE, which are responsible for AGS. This work presents an immunotherapy based on polymeric αGal-glycoconjugates for potentially treating allergic disorders by selectively inhibiting anti-αGal IgE antibodies. We synthesized a set of αGal-glycoconjugates, based on poly-L-lysine of different degrees of polymerization (DP1000, DP600, and DP100), to specifically inhibit in vitro the anti-αGal IgE antibodies in the serum of αGal-sensitized patients (n=13). Moreover, an animal model for αGal sensitization in GalT-KO mice was developed by intradermal administration of hard tick' salivary gland extract, mimicking the sensitization mechanism postulated in humans. The in vitro exposure to all polymeric glycoconjugates (5-10-20-50-100 µg/mL) mainly inhibited anti-αGal IgE and IgM isotypes, with a lower inhibition effect on the IgA and IgG, respectively. We demonstrated a differential anti-αGal isotype inhibition as a function of the length of the poly-L-lysine and the number of αGal residues exposed in the glycoconjugates. These results defined a minimum of 27 αGal residues to inhibit most of the induced anti-αGal IgE in vitro. Furthermore, the αGal-glycoconjugate DP1000-RA0118 (10 mg/kg sc.) showed a high capacity to remove the anti-αGal IgE antibodies (≥75% on average) induced in GalT-KO mice, together with similar inhibition for circulating anti-αGal IgG and IgM. Our study suggests the potential clinical use of poly-L-lysine-based αGal-glycoconjugates for treating allergic disorders mediated by anti-αGal IgE antibodies.
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Affiliation(s)
- Sara Olivera-Ardid
- RemAb Therapeutics, Mòdul de Recerca B, UAB Bellaterra, Barcelona, Spain
| | - Daniel Bello-Gil
- RemAb Therapeutics, Mòdul de Recerca B, UAB Bellaterra, Barcelona, Spain
| | - Alexander Tuzikov
- Department of Chemical Biology of Glycans and Lipids, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, Russia
| | - Ricardo N. Araujo
- Laboratório de Artrópodes Hematófagos, Departamento de Parasitologia, ICB/UFMG, Belo Horizonte, Brazil
| | - Yara Ferrero-Alves
- RemAb Therapeutics, Mòdul de Recerca B, UAB Bellaterra, Barcelona, Spain
| | - Blanca Esther García Figueroa
- MEGA: Asthma Inception and Progression Mechanisms, Complejo Hospitalario de Navarra (CHN), Pamplona, Spain
- Instituto de investigación sanitaria de Navarra (IdiSNA), Pamplona, Spain
- ARADyAL Research Network, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Moisés Labrador-Horrillo
- ARADyAL Research Network, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
- Allergy Section, Internal Medicine Department, Hospital Universitari Vall d’Hebron (HUVH), Barcelona, Spain
- Immunomediated Diseases and Innovative Therapies, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
| | - Ana L. García-Pérez
- Departamento de Sanidad Animal, Instituto Vasco de Investigación de Desarrollo Agrario (NEIKER), Derio, Spain
| | - Nicolai Bovin
- Department of Chemical Biology of Glycans and Lipids, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, Russia
| | - Rafael Mañez
- RemAb Therapeutics, Mòdul de Recerca B, UAB Bellaterra, Barcelona, Spain
- Hospital Universitari de Bellvitge, Servicio de Medicina Intensiva, Hospitalet de Llobregat, Barcelona, Spain
- Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Grupo Inmunidad Innata y Patología del Paciente Crítico, Hospitalet de Llobregat, Barcelona, Spain
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Frątczak M, Petko B, Sliwowska JH, Szeptycki J, Tryjanowski P. Similar Trajectories in Current Alcohol Consumption and Tick-Borne Diseases: Only Parallel Changes in Time or Links Between? Front Cell Infect Microbiol 2022; 11:790938. [PMID: 34976865 PMCID: PMC8716731 DOI: 10.3389/fcimb.2021.790938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 11/25/2021] [Indexed: 11/30/2022] Open
Abstract
In a modern world, both tick-borne diseases and alcohol consumption are among major public health threats. In the present opinion article, we pose the question, whether these two health problems: alcohol consumption and tick-borne diseases prevalence can be related. We hypothesize that it is possible due to at least three factors: outdoor places chosen for alcohol consumption, behavioral changes induced by alcohol, and possible stronger attraction of human hosts after alcohol consumption to ticks. Many important clues are coming from social studies about people’s preference of places to consume alcohol and from studies regarding the attraction of people consuming alcohol to mosquitos. These data, however, cannot be directly transferred to the case of alcohol consumption and ticks. Therefore, we suggest that more detailed studies are needed to better understand the possible individual attractiveness of people to ticks and ways alcohol may influence it.
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Affiliation(s)
- Martyna Frątczak
- Department of Zoology, Poznań University of Life Sciences, Poznań, Poland
| | - Branislav Petko
- Department of Zoology, Poznań University of Life Sciences, Poznań, Poland.,The University of Veterinary Medicine and Pharmacy in Košice, Košice, Slovakia
| | - Joanna H Sliwowska
- Department of Zoology, Poznań University of Life Sciences, Poznań, Poland
| | - Jan Szeptycki
- Department of Preclinical Sciences and Infectious Diseases, Poznań University of Life Sciences, Poznań, Poland
| | - Piotr Tryjanowski
- Department of Zoology, Poznań University of Life Sciences, Poznań, Poland
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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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Sharma SR, Crispell G, Mohamed A, Cox C, Lange J, Choudhary S, Commins SP, Karim S. Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism. Front Cell Infect Microbiol 2021; 11:775371. [PMID: 34926322 PMCID: PMC8671611 DOI: 10.3389/fcimb.2021.775371] [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: 09/13/2021] [Accepted: 10/27/2021] [Indexed: 11/16/2022] Open
Abstract
Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-α-1, 3-galactose (α-gal) injected into humans from the lone-star tick (Amblyomma americanum) bite. Indeed, α-gal is discovered in salivary glands of lone-star tick; however, the tick's specific intrinsic factors involved in endogenous α-gal production and presentation to host during hematophagy are poorly understood. This study aimed to investigate the functional role of two tick enzymes, α-D-galactosidase (ADGal) and β-1,4 galactosyltransferases (β-1,4GalT), in endogenous α-gal production, carbohydrate metabolism, and N-glycan profile in lone-star tick. The ADGal enzyme cleaves terminal α-galactose moieties from glycoproteins and glycolipids, whereas β-1,4GalT transfers α-galactose to a β1,4 terminal linkage acceptor sugars-GlcNAc, Glc, and Xyl-in various processes of glycoconjugate synthesis. An RNA interference approach was utilized to silence ADGal and β-1,4GalT in Am. americanum to examine their function in α-gal metabolism in tick and AGS onset. Silencing of ADGal led to the significant downregulation of genes involved in galactose metabolism and transport in Am. americanum. Immunoblot and N-glycan analysis of the Am. americanum salivary glands showed a significant reduction in α-gal levels in silenced tissues. However, there was no significant difference in the level of α-gal in β-1,4GalT-silenced tick salivary glands. A basophil-activation test showed a decrease in the frequency of activated basophil by ADGal-silenced salivary glands. These results provide an insight into the roles of ADGal and β-1,4GalT in α-gal production and presentation in ticks and the probable involvement in the onset of AGS.
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Affiliation(s)
- Surendra Raj Sharma
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
| | - Gary Crispell
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
| | - Ahmed Mohamed
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
| | - Cameron Cox
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
| | - Joshua Lange
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
| | - Shailesh Choudhary
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | - Scott P. Commins
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | - Shahid Karim
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
- Center for Molecular and Cellular Biosciences, The University of Southern Mississippi, Hattiesburg, MS, United States
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26
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Wolaver W, Thakrar S, Thomas K, Thakrar H, Schwartz L, Zuelzer W, Butterworth J, Hoelting K. Demystifying α-gal syndrome: identification and risk management in the perioperative setting. Curr Opin Anaesthesiol 2021; 34:761-765. [PMID: 34636791 DOI: 10.1097/aco.0000000000001066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW α-Gal syndrome is among a vexing perioperative consideration for anesthesiologists. Commonly referred to as 'red meat allergy', α-Gal syndrome is precipitated by a lone star tick bite resulting in the formation of immunoglobulin E (IgE) antibodies against the tick salivary glycoproteins and noncatarrhine mammalian tissue. RECENT FINDINGS Up to 20% of the population in the southeastern United States may test positive for IgE antibodies to α-Gal. Increasingly, recognition of α-Gal syndrome as an immune response to red meat consumption and certain drugs, many of which may be administered within the perioperative period, has led to greater awareness of the insidious nature of its presentation - from mild urticaria and gastrointestinal symptoms to severe anaphylaxis. SUMMARY With the increasing prevalence and identification of α-Gal syndrome, a safe and tailored perioperative process is needed to integrate a pathway that involves multidisciplinary communication, robust information sharing platform, and a structured peri-procedure management.
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Affiliation(s)
- Whitney Wolaver
- Department of Anesthesiology, Virginia Commonwealth University Health System, Richmond, Virginia
| | - Shilen Thakrar
- Department of Anesthesiology, Virginia Commonwealth University Health System, Richmond, Virginia
| | - Kelvin Thomas
- Department of Anesthesiology, Virginia Commonwealth University Health System, Richmond, Virginia
| | - Hiral Thakrar
- Department of Allergy and Immunology, Scripps Health Carmel Valley, San Diego, California
| | | | | | - John Butterworth
- Department of Anesthesiology, Virginia Commonwealth University Health System, Richmond, Virginia
| | - Kyle Hoelting
- Department of Pharmacy Services, Virginia Commonwealth University Health System, Richmond, Virginia, USA
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27
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Apari P, Földvári G. Tick bite induced α-gal syndrome highlights anticancer effect of allergy. Bioessays 2021; 44:e2100142. [PMID: 34811781 DOI: 10.1002/bies.202100142] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 11/03/2021] [Accepted: 11/05/2021] [Indexed: 01/05/2023]
Abstract
Tick bite induced α-gal syndrome (AGS) following consumption of mammalian meat is a recently described intriguing disease occurring worldwide. Here we argue that AGS and delayed allergy in general is an adaptive defence method against cancer. Our hypothesis synthesizes two lines of supporting evidence. First, allergy has been shown to have direct anti-cancer effects with unknown mechanism. Second, eating processed meat was shown to be linked to developing cancer. Humans lost their genes encoding molecules α-gal 30 MYA and Neu5Gc 2 MYA, the latter co-occurring with the start of using fire. These molecules are acquired from external sources, as tick bite for α-gal and mammalian meat for Neu5Gc, the latter accumulating in tumors. The resulting specific delayed allergic response is a molecular adaptation to fight cancer. By further testing and applying our hypothesis, new avenues in cancer research and therapy will open that might save lives and decrease human suffering.
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Affiliation(s)
- Péter Apari
- Institute of Evolution, Centre for Ecological Research, Budapest, Hungary
| | - Gábor Földvári
- Institute of Evolution, Centre for Ecological Research, Budapest, Hungary
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28
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Katiyar KS, Burrell JC, Laimo FA, Browne KD, Bianchi JR, Walters A, Ayares DL, Smith DH, Ali ZS, Ledebur HC, Cullen DK. Biomanufacturing of Axon-Based Tissue Engineered Nerve Grafts Using Porcine GalSafe Neurons. Tissue Eng Part A 2021; 27:1305-1320. [PMID: 33514288 PMCID: PMC8610031 DOI: 10.1089/ten.tea.2020.0303] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 01/11/2021] [Indexed: 12/14/2022] Open
Abstract
Existing strategies for repair of major peripheral nerve injury (PNI) are inefficient at promoting axon regeneration and functional recovery and are generally ineffective for nerve lesions >5 cm. To address this need, we have previously developed tissue engineered nerve grafts (TENGs) through the process of axon stretch growth. TENGs consist of living, centimeter-scale, aligned axon tracts that accelerate axon regeneration at rates equivalent to the gold standard autograft in small and large animal models of PNI, by providing a newfound mechanism-of-action referred to as axon-facilitated axon regeneration (AFAR). To enable clinical-grade biomanufacturing of TENGs, a suitable cell source that is hypoimmunogenic, exhibits low batch-to-batch variability, and able to tolerate axon stretch growth must be utilized. To fulfill these requirements, a genetically engineered, FDA-approved, xenogeneic cell source, GalSafe® neurons, produced by Revivicor, Inc., have been selected to advance TENG biofabrication for eventual clinical use. To this end, sensory and motor neurons were harvested from genetically engineered GalSafe day 40 swine embryos, cultured in custom mechanobioreactors, and axon tracts were successfully stretch-grown to 5 cm within 25 days. Importantly, both sensory and motor GalSafe neurons were observed to tolerate established axon stretch growth regimes of ≥1 mm/day to produce continuous, healthy axon tracts spanning 1, 3, or 5 cm. Once stretch-grown, 1 cm GalSafe TENGs were transplanted into a 1 cm lesion in the sciatic nerve of athymic rats. Regeneration was assessed through histological measures at the terminal time point of 2 and 8 weeks. Neurons from GalSafe TENGs survived and elicited AFAR as observed when using wild-type TENGs. At 8 weeks postrepair, myelinated regenerated axons were observed in the nerve section distal to the injury site, confirming axon regeneration across the lesion. These experiments are the first to demonstrate successful harvest and axon stretch growth of GalSafe neurons for use as starting biomass for bioengineered nerve grafts as well as initial safety and efficacy in an established preclinical model-important steps for the advancement of clinical-grade TENGs for future regulatory testing and eventual clinical trials. Impact statement Biofabrication of tissue engineered medical products requires several steps, one of which is choosing a suitable starting biomass. To this end, we have shown that the clinical-grade, genetically engineered biomass-GalSafe® neurons-is a viable option for biomanufacturing of our tissue engineered nerve grafts (TENGs) to promote regeneration following major peripheral nerve injury. Importantly, this is a first step in clinical-grade TENG biofabrication, proving that GalSafe TENGs recapitulate the mechanism of axon-facilitated axon regeneration seen previously with research-grade TENGs.
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Affiliation(s)
- Kritika S. Katiyar
- Axonova Medical, LLC, Philadelphia, Pennsylvania, USA
- Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
| | - Justin C. Burrell
- Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
| | - Franco A. Laimo
- Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
| | - Kevin D. Browne
- Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
| | | | | | | | - Douglas H. Smith
- Axonova Medical, LLC, Philadelphia, Pennsylvania, USA
- Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Zarina S. Ali
- Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
| | - Harry C. Ledebur
- Axonova Medical, LLC, Philadelphia, Pennsylvania, USA
- Battelle Memorial Institute, Columbus, Ohio, USA
| | - D. Kacy Cullen
- Axonova Medical, LLC, Philadelphia, Pennsylvania, USA
- Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
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Epelboin L, Roche F, Dueymes M, Guillot G, Duron O, Nacher M, Djossou F, Soria A. Allergy to Mammalian Meat Linked to Alpha-Gal Syndrome Potentially After Tick Bite in the Amazon: A Case Series. Am J Trop Med Hyg 2021; 105:1396-1403. [PMID: 34544046 PMCID: PMC8592224 DOI: 10.4269/ajtmh.20-1630] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 04/19/2021] [Indexed: 12/11/2022] Open
Abstract
The past decade has seen the emergence of a new type of food allergy occurring after ingestion of mammalian meat. This allergy is related to immunoglobulin (Ig)E specific for galactose-alpha-1,3 galactose (α-Gal). Originally described in the United States in 2009, other cases have subsequently been described in Australia and in Europe, but still very few in Latin America. The purpose of this study was to show the existence of this pathology in French Guiana and to describe the historical, clinical, and biological characteristics of these patients. Patients reporting an allergy to mammalian meat were included between September 2017 and August 2019. Eleven patients were included, nine of whom exhibited digestive symptoms; four, urticaria reactions; three, respiratory reactions; and five angioedema. The time between ingestion of red meat and reaction varied between 1.5 and 6 hours. The implicated meats were most often beef and pork. All patients had been regularly exposed to tick bites before the appearance of symptoms. All the samples (n = 7) were positive for anti-α-Gal anti-mammalian meats IgE. All the patients were Caucasian French expatriates. This study confirms the presence of this new entity in French Guiana and is the largest reported in Latin America. Our results do not clearly allow us to state that tick bites are the cause of this allergy, but all patients reported being exposed regularly to these arthropods.
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Affiliation(s)
- Loïc Epelboin
- Infectious and Tropical Diseases Department, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana.,Equipe EA 3593, Ecosystèmes Amazoniens et Pathologie Tropicale, Université de la Guyane, Cayenne, French Guiana.,Centre d'Investigation Clinique, INSERM 1424, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana
| | - Florent Roche
- Université des Antilles et de la Guyane, Faculté de Médecine Hyacinthe Basturaud, Pointe-à-Pitre, France
| | - Maryvonne Dueymes
- Equipe EA 3593, Ecosystèmes Amazoniens et Pathologie Tropicale, Université de la Guyane, Cayenne, French Guiana.,Laboratory of Medical Biology, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana
| | - Geneviève Guillot
- Department of Pneumology and Gastroenterology, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana
| | - Olivier Duron
- Maladies Infectieuses et Vecteurs: Écologie, Génétique, Évolution et Contrôle, Centre National de la Recherche Scientifique, Institut pour la Recherche et le Développement, Université de Montpellier, Montpellier, France
| | - Mathieu Nacher
- Centre d'Investigation Clinique, INSERM 1424, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana
| | - Félix Djossou
- Infectious and Tropical Diseases Department, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana.,Equipe EA 3593, Ecosystèmes Amazoniens et Pathologie Tropicale, Université de la Guyane, Cayenne, French Guiana
| | - Angèle Soria
- Tenon Hospital, Dermatology-Allergology Department, Sorbonne University, Paris, France
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30
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Precision medicine in clinical oncology: the journey from IgG antibody to IgE. Curr Opin Allergy Clin Immunol 2021; 20:282-289. [PMID: 32349107 DOI: 10.1097/aci.0000000000000637] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
PURPOSE OF REVIEW Cancer is one of the leading causes of death and the incidence rates are constantly rising. The heterogeneity of tumors poses a big challenge for the treatment of the disease and natural antibodies additionally affect disease progression. The introduction of engineered mAbs for anticancer immunotherapies has substantially improved progression-free and overall survival of cancer patients, but little efforts have been made to exploit other antibody isotypes than IgG. RECENT FINDINGS In order to improve these therapies, 'next-generation antibodies' were engineered to enhance a specific feature of classical antibodies and form a group of highly effective and precise therapy compounds. Advanced antibody approaches include among others antibody-drug conjugates, glyco-engineered and Fc-engineered antibodies, antibody fragments, radioimmunotherapy compounds, bispecific antibodies and alternative (non-IgG) immunoglobulin classes, especially IgE. SUMMARY The current review describes solutions for the needs of next-generation antibody therapies through different approaches. Careful selection of the best-suited engineering methodology is a key factor in developing personalized, more specific and more efficient mAbs against cancer to improve the outcomes of cancer patients. We highlight here the large evidence of IgE exploiting a highly cytotoxic effector arm as potential next-generation anticancer immunotherapy.
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31
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Murangi T, Prakash P, Moreira BP, Basera W, Botha M, Cunningham S, Facey-Thomas H, Halajian A, Joshi L, Ramjith J, Falcone FH, Horsnell W, Levin ME. Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome. J Allergy Clin Immunol 2021; 149:698-707.e3. [PMID: 34333031 DOI: 10.1016/j.jaci.2021.07.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 06/23/2021] [Accepted: 07/13/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND IgE to galactose alpha-1,3 galactose (alpha-gal) causes alpha-gal syndrome (delayed anaphylaxis after ingestion of mammalian meat). Development of sensitization has been attributed to tick bites; however, the possible role of other parasites has not been well studied. OBJECTIVE Our aims were to assess the presence, relative abundances, and site of localization of alpha-gal-containing proteins in common ectoparasites and endoparasites endemic in an area of high prevalence of alpha-gal syndrome, as well as to investigate the ability of ascaris antigens to elicit a reaction in a humanized rat basophil in vitro sensitization model. METHODS Levels of total IgE, Ascaris-specific IgE, and alpha-gal IgE were measured in sera from patients with challenge-proven alpha-gal syndrome and from controls without allergy. The presence, concentration, and localization of alpha-gal in parasites were assessed by ELISA, Western blotting, and immunohistochemistry. The ability of Ascaris lumbricoides antigen to elicit IgE-dependent reactivity was demonstrated by using the RS-ATL8 basophil reporter system. RESULTS Alpha-gal IgE level correlated with A lumbricoides-specific IgE level. Alpha-gal protein at 70 to 130 kDa was detected in A lumbricoides at concentrations higher than those found in Rhipicephalus evertsi and Amblyomma hebraeum ticks. Immunohistochemistry was used to localize alpha-gal in tick salivary acini and the helminth gut. Non-alpha-gal-containing A lumbricoides antigens activated RS-ATL8 basophils primed with serum from subjects with alpha-gal syndrome. CONCLUSION We demonstrated the presence, relative abundances, and site of localization of alpha-gal-containing proteins in parasites. The activation of RS-ATL8 IgE reporter cells primed with serum from subjects with alpha-gal syndrome on exposure to non-alpha-gal-containing A lumbricoides proteins indicates a possible role of exposure to A lumbricoides in alpha-gal sensitization and clinical reactivity.
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Affiliation(s)
- Tatenda Murangi
- Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, Division of immunology, University of Cape Town, Cape Town, South Africa
| | - Prema Prakash
- Institute of Parasitology, Biomedical Research Center Seltersberg, Justus Liebig University Giessen, Giessen, Germany
| | - Bernardo Pereira Moreira
- Institute of Parasitology, Biomedical Research Center Seltersberg, Justus Liebig University Giessen, Giessen, Germany
| | - Wisdom Basera
- School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; Burden of Disease Research Unit, South African Medical Research Council, Cape Town, South Africa
| | - Maresa Botha
- Division of Paediatric Allergy, Department of Paediatrics, University of Cape Town, Cape Town, South Africa
| | - Stephen Cunningham
- Glycoscience Group, Biomedical Sciences, National University of Ireland Galway, Galway, Ireland
| | - Heidi Facey-Thomas
- Division of Paediatric Allergy, Department of Paediatrics, University of Cape Town, Cape Town, South Africa
| | - Ali Halajian
- Research Administration and Development, University of Limpopo, Sovenga, South Africa
| | - Lokesh Joshi
- Glycoscience Group, Biomedical Sciences, National University of Ireland Galway, Galway, Ireland
| | - Jordache Ramjith
- Department for Health Evidence, Biostatistics Research Group, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Franco H Falcone
- Institute of Parasitology, Biomedical Research Center Seltersberg, Justus Liebig University Giessen, Giessen, Germany
| | - William Horsnell
- Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, Division of immunology, University of Cape Town, Cape Town, South Africa; Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Michael E Levin
- Division of Paediatric Allergy, Department of Paediatrics, University of Cape Town, Cape Town, South Africa.
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32
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Sharma SR, Karim S. Tick Saliva and the Alpha-Gal Syndrome: Finding a Needle in a Haystack. Front Cell Infect Microbiol 2021; 11:680264. [PMID: 34354960 PMCID: PMC8331069 DOI: 10.3389/fcimb.2021.680264] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 06/29/2021] [Indexed: 01/01/2023] Open
Abstract
Ticks and tick-borne diseases are significant public health concerns. Bioactive molecules in tick saliva facilitate prolonged blood-feeding and transmission of tick-borne pathogens to the vertebrate host. Alpha-gal syndrome (AGS), a newly reported food allergy, is believed to be induced by saliva proteins decorated with a sugar molecule, the oligosaccharide galactose-⍺-1,3-galactose (α-gal). This syndrome is characterized by an IgE antibody-directed hypersensitivity against α-gal. The α-gal antigen was discovered in the salivary glands and saliva of various tick species including, the Lone Star tick (Amblyomma americanum). The underlying immune mechanisms linking tick bites with α-gal-specific IgE production are poorly understood and are crucial to identify and establish novel treatments for this disease. This article reviews the current understanding of AGS and its involvement with tick species.
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Affiliation(s)
- Surendra Raj Sharma
- Center for Molecular and Cellular Biology, School of Biological, Environmental, and Earth Sciences, University of Southern Mississippi, Hattiesburg, MS, United States
| | - Shahid Karim
- Center for Molecular and Cellular Biology, School of Biological, Environmental, and Earth Sciences, University of Southern Mississippi, Hattiesburg, MS, United States
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33
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Comparative immunogenicity of decellularized wild type and alpha 1,3 galactosyltransferase knockout pig lungs. Biomaterials 2021; 276:121029. [PMID: 34311317 DOI: 10.1016/j.biomaterials.2021.121029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/08/2021] [Accepted: 07/13/2021] [Indexed: 12/23/2022]
Abstract
Decellularized pig lungs recellularized with human lung cells offer a novel approach for organ transplantation. However, the potential immunogenicity of decellularized pig lungs following exposure to human tissues has not been assessed. We found that exposure of native lungs from wildtype and transgenic pigs lacking alpha (1,3)-galactosyltransferase (α-gal KO) to sera from normal healthy human volunteers demonstrated similar robust IgM and IgG immunoreactivity, comparably decreased in decellularized lungs. Similar results were observed with sera from patients who had previously undergone transcutaneous porcine aortic valve replacement (TAVR) or from patients with increased circulating anti-α-gal IgE antibodies (α-gal syndrome). Depleting anti-α-gal antibodies from the sera demonstrated both specificity of α-gal immunoreactivity and also residual immunoreactivity similar between wildtype and α-gal KO pig lungs. Exposure of human monocytes and macrophages to native wildtype lungs demonstrated greater induction of M2 phenotype than native α-gal KO pig lungs, which was less marked with decellularized lungs of either type. Overall, these results demonstrate that native wildtype and α-gal KO pig lungs provoke similar immune responses that are comparably decreased following decellularization. This provides a further platform for potential use of decellularized pig lungs in tissue engineering approaches and subsequent transplantation schemes but no obvious overall immunologic advantage of utilizing lungs obtained from α-gal KO pigs.
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34
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Bansal RA, Bahal S, O'Brien R, Miller J, Bansal AS, Yong PF. The first reported cases of meat allergy following tick bites in the UK. JRSM Open 2021; 12:2054270421996131. [PMID: 33996105 DOI: 10.1177/2054270421996131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Allergic reactions frequently involve the production of immunoglobulin E (IgE) antibodies to proteins. However, reactions directed against carbohydrate moieties are increasingly being recognised. Tick bites can contribute to the development of immunoglobulin E to the galactose-1,3-galactose (alpha-gal) moiety on tick salivary proteins. These IgE molecules can cross-react with alpha-gal found in red meats, causing Type I IgE-mediated hypersensitivity reactions to these foods. We present three cases of delayed reactions to beef, pork and lamb in patients with prior tick bites and in the presence of a positive-specific IgE to alpha-gal. Patients were advised to avoid red meat consumption and to carry emergency treatment in the form of anti-histamines with or without adrenaline autoinjector devices. This is the first published report of red meat allergy caused by tick bites suffered in the UK.
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Affiliation(s)
- Rhea A Bansal
- Immunology Department, Frimley Park Hospital, Frimley Health NHS Trust, Frimley GU16 7UJ, UK
| | - Sameer Bahal
- Immunology Department, The Royal Free Hospital, Royal Free London NHS Foundation Trust, London NW3 2QG, UK
| | - Rachael O'Brien
- Immunology Department, Frimley Park Hospital, Frimley Health NHS Trust, Frimley GU16 7UJ, UK
| | - Joanne Miller
- Immunology Department, Royal Surrey County Hospital, Royal Surrey NHS Foundation Trust, Surrey GU2 7XX, UK
| | | | - Patrick Fk Yong
- Immunology Department, Frimley Park Hospital, Frimley Health NHS Trust, Frimley GU16 7UJ, UK.,Immunology Department, Royal Surrey County Hospital, Royal Surrey NHS Foundation Trust, Surrey GU2 7XX, UK
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35
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Beltrán-Cárdenas CE, Granda-Restrepo DM, Franco-Aguilar A, Lopez-Teros V, Arvizu-Flores AA, Cárdenas-Torres FI, Ontiveros N, Cabrera-Chávez F, Arámburo-Gálvez JG. Prevalence of Food-Hypersensitivity and Food-Dependent Anaphylaxis in Colombian Schoolchildren by Parent-Report. ACTA ACUST UNITED AC 2021; 57:medicina57020146. [PMID: 33562800 PMCID: PMC7915673 DOI: 10.3390/medicina57020146] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/24/2021] [Accepted: 01/27/2021] [Indexed: 11/16/2022]
Abstract
Background and objectives: The epidemiology of food allergy (FA) and food-dependent anaphylaxis remains unknown in Colombia. Our aim was to estimate by parent-report the prevalence of FA and food-dependent anaphylaxis in a Colombian population of schoolchildren. Materials and methods: A printed questionnaire was sent to parents of schoolchildren aged 5–12 years old from Medellín, Colombia in order to collect FA-related data. Results: Nine hundred and sixty-nine (969) parents returned the questionnaire with valid responses (response rate, 52.5%). The estimated prevalence rates (95% CI) were: adverse food reactions 12.79% (10.76–15.07), “perceived FA, ever” 10.93% (9.08–13.08), “physician-diagnosed FA, ever” 4.33% (3.14–5.81), “immediate-type FA, ever” 6.81% (5.30–8.58), “immediate-type FA, current” 3.30% (2.26–4.63), and food-dependent anaphylaxis 1.85% (1.10–2.92). The most frequently reported food allergens were milk (1.44%), fruits (0.41%), meat (0.41%), and peanut (0.3%). Sixty-one percent of “food-dependent anaphylaxis” cases sought medical attention, but only eleven percent of the cases reported the prescription of an epinephrine autoinjector. Conclusions: FA and food-dependent anaphylaxis are not uncommon among schoolchildren from Colombia. The prescription of epinephrine autoinjectors should be encouraged among health personnel for the optimal management of suspected cases of food-dependent anaphylaxis.
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Affiliation(s)
- Carlos Eduardo Beltrán-Cárdenas
- Postgraduate Program in Nutrition Sciences, Faculty of Nutrition Sciences, University of Sinaloa, Culiacan, Sinaloa 80019, Mexico; (C.E.B.-C.); (F.I.C.-T.)
| | - Diana María Granda-Restrepo
- Food Department, Faculty of Pharmaceutical and Food Sciences, University of Antioquia, Medellín, Antioquia 50010, Colombia; (D.M.G.-R.); (A.F.-A.)
| | - Alejandro Franco-Aguilar
- Food Department, Faculty of Pharmaceutical and Food Sciences, University of Antioquia, Medellín, Antioquia 50010, Colombia; (D.M.G.-R.); (A.F.-A.)
| | - Veronica Lopez-Teros
- Postgraduate Program in Health Sciences, Division of Biological and Health Sciences, University of Sonora, Hermosillo, Sonora 83000, Mexico; (V.L.-T.); (A.A.A.-F.)
| | - Aldo Alejandro Arvizu-Flores
- Postgraduate Program in Health Sciences, Division of Biological and Health Sciences, University of Sonora, Hermosillo, Sonora 83000, Mexico; (V.L.-T.); (A.A.A.-F.)
| | - Feliznando Isidro Cárdenas-Torres
- Postgraduate Program in Nutrition Sciences, Faculty of Nutrition Sciences, University of Sinaloa, Culiacan, Sinaloa 80019, Mexico; (C.E.B.-C.); (F.I.C.-T.)
| | - Noé Ontiveros
- Clinical and Research Laboratory (LACIUS, URS), Department of Chemical, Biological, and Agricultural Sciences (DC-QB), Division of Sciences and Engineering, University of Sonora, Navojoa, Sonora 85880, Mexico;
| | - Francisco Cabrera-Chávez
- Postgraduate Program in Nutrition Sciences, Faculty of Nutrition Sciences, University of Sinaloa, Culiacan, Sinaloa 80019, Mexico; (C.E.B.-C.); (F.I.C.-T.)
- Correspondence: (F.C.-C.); (J.G.A.-G.)
| | - Jesús Gilberto Arámburo-Gálvez
- Postgraduate Program in Nutrition Sciences, Faculty of Nutrition Sciences, University of Sinaloa, Culiacan, Sinaloa 80019, Mexico; (C.E.B.-C.); (F.I.C.-T.)
- Postgraduate Program in Health Sciences, Division of Biological and Health Sciences, University of Sonora, Hermosillo, Sonora 83000, Mexico; (V.L.-T.); (A.A.A.-F.)
- Correspondence: (F.C.-C.); (J.G.A.-G.)
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Nkurunungi G, Mpairwe H, Versteeg SA, Diepen A, Nassuuna J, Kabagenyi J, Nambuya I, Sanya RE, Nampijja M, Serna S, Reichardt N, Hokke CH, Webb EL, Ree R, Yazdanbakhsh M, Elliott AM. Cross-reactive carbohydrate determinant-specific IgE obscures true atopy and exhibits ⍺-1,3-fucose epitope-specific inverse associations with asthma. Allergy 2021; 76:233-246. [PMID: 32568414 PMCID: PMC7610925 DOI: 10.1111/all.14469] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 05/03/2020] [Accepted: 06/03/2020] [Indexed: 12/22/2022]
Abstract
Background In high-income, temperate countries, IgE to allergen extracts is a risk factor for, and mediator of, allergy-related diseases (ARDs). In the tropics, positive IgE tests are also prevalent, but rarely associated with ARD. Instead, IgE responses to ubiquitous cross-reactive carbohydrate determinants (CCDs) on plant, insect and parasite glycoproteins, rather than to established major allergens, are dominant. Because anti-CCD IgE has limited clinical relevance, it may impact ARD phenotyping and assessment of contribution of atopy to ARD. Methods Using an allergen extract-based test, a glycan and an allergen (glyco)protein microarray, we mapped IgE fine specificity among Ugandan rural Schistosoma mansoni (Sm)-endemic communities, proximate urban communities, and importantly in asthmatic and nonasthmatic schoolchildren. Results Overall, IgE sensitization to extracts was highly prevalent (43%-73%) but allergen arrays indicated that this was not attributable to established major allergenic components of the extracts (0%-36%); instead, over 40% of all participants recognized CCD-bearing components. Using glycan arrays, we dissected IgE responses to specific glycan moieties and found that reactivity to classical CCD epitopes (core β-1,2-xylose, α-1,3-fucose) was positively associated with sensitization to extracts, rural environment and Sm infection, but not with skin reactivity to extracts or sensitization to their major allergenic components. Interestingly, we discovered that reactivity to only a subset of core α-1,3-fucose-carrying N-glycans was inversely associated with asthma. Conclusions CCD reactivity is not just an epiphenomenon of parasite exposure hampering specificity of allergy diagnostics; mechanistic studies should investigate whether specific CCD moieties identified here are implicated in the protective effect of certain environmental exposures against asthma.
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Affiliation(s)
- Gyaviira Nkurunungi
- Immunomodulation and Vaccines Programme Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit Entebbe Uganda
- Department of Clinical Research London School of Hygiene and Tropical Medicine London UK
| | - Harriet Mpairwe
- Immunomodulation and Vaccines Programme Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit Entebbe Uganda
| | - Serge A. Versteeg
- Departments of Experimental Immunology and of Otorhinolaryngology Amsterdam University Medical Centers (AMC) Amsterdam The Netherlands
| | - Angela Diepen
- Department of Parasitology Leiden University Medical Center Leiden The Netherlands
| | - Jacent Nassuuna
- Immunomodulation and Vaccines Programme Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit Entebbe Uganda
| | - Joyce Kabagenyi
- Immunomodulation and Vaccines Programme Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit Entebbe Uganda
| | - Irene Nambuya
- Immunomodulation and Vaccines Programme Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit Entebbe Uganda
| | - Richard E. Sanya
- Immunomodulation and Vaccines Programme Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit Entebbe Uganda
- College of Health Sciences Makerere University Kampala Uganda
| | - Margaret Nampijja
- Immunomodulation and Vaccines Programme Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit Entebbe Uganda
| | - Sonia Serna
- Glycotechnology Laboratory Centro de Investigación Cooperativa en Biomateriales (CIC biomaGUNE) San Sebastián Spain
| | - Niels‐Christian Reichardt
- Glycotechnology Laboratory Centro de Investigación Cooperativa en Biomateriales (CIC biomaGUNE) San Sebastián Spain
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER‐BBN) San Sebastián Spain
| | - Cornelis H. Hokke
- Department of Parasitology Leiden University Medical Center Leiden The Netherlands
| | - Emily L. Webb
- Department of Infectious Disease Epidemiology London School of Hygiene and Tropical Medicine MRC Tropical Epidemiology Group London UK
| | - Ronald Ree
- Departments of Experimental Immunology and of Otorhinolaryngology Amsterdam University Medical Centers (AMC) Amsterdam The Netherlands
| | - Maria Yazdanbakhsh
- Department of Parasitology Leiden University Medical Center Leiden The Netherlands
| | - Alison M. Elliott
- Immunomodulation and Vaccines Programme Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit Entebbe Uganda
- Department of Clinical Research London School of Hygiene and Tropical Medicine London UK
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Baumann SA, Fritz C, Mueller RS. Food antigen-specific IgE in dogs with suspected food hypersensitivity. TIERAERZTLICHE PRAXIS AUSGABE KLEINTIERE HEIMTIERE 2020; 48:395-402. [PMID: 33276389 DOI: 10.1055/a-1274-9210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
OBJECTIVE Knowledge of cross-reactions in food-sensitive dogs will influence the choice of elimination diets and the long-term management of those patients. The objective of this study was to evaluate food allergen-specific IgE tests of suspected allergic dogs for concurrent positive reactions as possible evidence for cross reactions between allergens. MATERIAL AND METHODS Results of serum IgE tests from 760 suspected allergic dogs submitted to 2 laboratories were evaluated statistically. After the tested allergens were grouped by their phylogenetic relationship, odds ratios as well as a sensitivity analysis of the odds ratios were performed to evaluate if concurrent positive IgE results to 2 allergens occurred more often than expected. RESULTS Within related allergen pairs 27% (laboratory 1) and 72% (laboratory 2) of the pairs could be considered as associated. For the unrelated allergen pairs only 6.8% and 10.6% of the analyzed pairs were considered associated respectively. Strong correlations were shown in the group of ruminant allergens, especially beef and lamb, and grain allergens. High rates of concurrent reactions were also detected in the poultry group, especially between chicken and duck, as well as between pork and ruminant allergens, and soy and grain allergens. CONCLUSION As our results showed not only correlations within related but also between non-related allergens, the possible relevance of carbohydrate moieties as well as panallergens for canine hypersensitivities warrants further study. Further investigations are necessary to distinguish co-sensitization from cross-reactions and determine the clinical relevance of food-specific IgE reactivity. CLINICAL RELEVANCE Due to possible cross reactivity related allergens, especially beef and lamb as well as grain allergens, should not be used for an elimination diet to avoid false results.
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Affiliation(s)
- Sandra A Baumann
- Small Animal Medicine Clinic, Centre for Clinical Veterinary Medicine, Ludwig Maximilian University
| | | | - Ralf S Mueller
- Small Animal Medicine Clinic, Centre for Clinical Veterinary Medicine, Ludwig Maximilian University
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Abstract
Red meat allergies have followed tick bites on every continent except Antarctica. The sensitizing antigen is galactose-α-1,3-galactose (α-gal), an oligosaccharide constituent of nonprimate blood and meat, acquired by ticks during animal bloodfeeding. Because red meat allergy after tick bites is a worldwide phenomenon, the objectives of this review were to describe the global epidemiology of red meat allergy after tick bites and its immunological mechanisms; to identify the human risk factors for red meat allergy after tick bites; to identify the most common tick vectors of red meat allergy worldwide; to describe the clinical manifestations, diagnostic confirmation, and management of patients with red meat allergy after tick bites; and to recommend strategies for the prevention of tick bites. To meet these objectives, Internet search engines were queried with keywords to select scientific articles for review. The keywords included ticks, tick bites, allergy, anaphylaxis, and meat allergy. The study period was defined as 1980-2019. The major risk factors for red meat allergy after tick bites included male sex, non-B blood type, systemic mastocytosis, a bioprosthetic (bovine or porcine) heart valve, and preexisting allergies to gelatin or animal dander. Following confirmation by challenge testing, patients with red meat allergies should avoid red meats, foods containing gelatin, and intravenous immunotherapy with monoclonal antibodies such as cetuximab and infliximab produced in SP2/0 mouse cell lines. Red meat allergy after tick bites represents an emerging threat from tick bites in addition to infectious diseases.
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Affiliation(s)
- James H Diaz
- From the School of Public Health, Environmental, and Occupational Health Sciences, Louisiana State University Health Sciences Center, New Orleans
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Shroba J, Rath N, Barnes C. Possible Role of Environmental Factors in the Development of Food Allergies. Clin Rev Allergy Immunol 2020; 57:303-311. [PMID: 30159849 DOI: 10.1007/s12016-018-8703-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
The development of food allergies is thought to involve multiple factors, and it is unclear which conveys the most risk regarding this process. Since food allergy is a chronic disease without a cure at this time, understanding its development could provide an avenue for preventive practices and development of a curative treatment. Both historical and current data implicate maternal factors, genetics, and environmental exposures as major risk factors in the development of food allergy. An immature gut of the infant has been hypothesized as a possible route of sensitization. Breastfeeding until at least 6 months of age has been shown to have protective factors for the newborn and may possibly improve gut permeability. Newer studies such as the LEAP and EAT investigations also looked at early exposure and prevention of food allergies; their long-term results are critical in understanding early introduction and tolerance. Cutaneous exposure, oral exposure, and food protein exposure in house dust with their relation to the food allergy course are also a path of interest. Current research has shown sensitization can occur through impaired skin such as those with eczema and a filaggrin mutation. Tropomyosin and alpha-gal also are related to the complicated immunomodulatory factors involved in food allergy and allergic response. Cross-reactivity with plant allergens, sensitization to house dust mite and cockroach, and lone star tick bites can also induce food allergens in children and adults. Together, these factors provide a cohesive beginning to understanding how food allergies can occur and can influence further investigation into prevention, treatment, and eventual cure of food allergies.
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Affiliation(s)
- Jodi Shroba
- Division of Allergy, Asthma and Immunology, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA.
| | - Niharika Rath
- Division of Allergy, Asthma and Immunology, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA
| | - Charles Barnes
- Division of Allergy, Asthma and Immunology, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA
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40
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Valk-Weeber RL, Eshuis-de Ruiter T, Dijkhuizen L, van Leeuwen SS. Dynamic Temporal Variations in Bovine Lactoferrin Glycan Structures. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:549-560. [PMID: 31829588 DOI: 10.1021/acs.jafc.9b06762] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
It has been reported previously that glycosylation of bovine lactoferrin changes over time. A detailed structural overview of these changes over the whole course of lactation, including predry period milk, is lacking. In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds. In addition, comparisons are made with commercial bovine lactoferrin samples. During the first 72 h, dynamic changes in lactoferrin glycosylation occurred. Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed. In some cows, we observed (α2,3)-linked sialic acid in the earliest colostrum samples. The glycoprofiles appeared stable from 1 month after delivery, as well as between cows. In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year. Lactoferrin glycosylation in the predry period resembles colostrum lactoferrin. The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
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Affiliation(s)
- Rivca L Valk-Weeber
- Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB) , University of Groningen , Nijenborgh 7 , 9747 AG Groningen , The Netherlands
| | | | - Lubbert Dijkhuizen
- Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB) , University of Groningen , Nijenborgh 7 , 9747 AG Groningen , The Netherlands
| | - Sander S van Leeuwen
- Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB) , University of Groningen , Nijenborgh 7 , 9747 AG Groningen , The Netherlands
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Fischer J, Huynh HN, Hebsaker J, Forchhammer S, Yazdi AS. Prevalence and Impact of Type I Sensitization to Alpha-Gal in Patients Consulting an Allergy Unit. Int Arch Allergy Immunol 2019; 181:119-127. [PMID: 31805569 DOI: 10.1159/000503966] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 10/07/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Alpha-gal syndrome is a complex allergy with high clinical relevance regarding mammalian-derived food and drugs and is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-α-1,3-galactose. As not all alpha-gal sIgE-positive individuals pre-sent clinical symptoms upon consumption of mammalian meat, the diagnostic value of alpha-gal sIgE has yet to be clarified. OBJECTIVE To investigate the prevalence of alpha-gal-sIgE positivity among allergy patients, examine the impact of tick bites as associated risk factors and determine the diagnostic value of alpha-gal-sIgE positivity. METHODS A retrospective cross-sectional study evaluating patients in the Allergy Unit was performed. Alpha-gal-sIgE levels were assessed by ImmunoCAP assay. Exposure to tick bites was assessed by a questionnaire. A receiver operating characteristics (ROC) curve analysis was performed to determine the diagnostic value of alpha-gal sIgE for the diagnosis of alpha-gal syndrome. RESULTS In the study population (n = 1369), the overall prevalence of alpha-gal-sIgE-positive (≥0.10 kUA/L) individuals was 19.9%, and the highest prevalence (30.2%) was found in patients with insect venom allergies. A reported tick bite within the 12 months prior to blood sampling significantly increased the risk of alpha-gal-sIgE positivity (OR 2.084). The ROC curve analysis indicated alpha-gal sIgE ≥0.54 kUA/L as the optimal cutoff point for assessing the diagnostic value of alpha-gal syndrome in allergy patients. CONCLUSIONS In allergy care settings, alpha-gal-sIgE positivity is a common finding. Alpha-gal sIgE is a sensitive marker in the diagnosis of alpha-gal syndrome but has limited predictive value for the characteristics or severity of this allergy.
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Affiliation(s)
- Jörg Fischer
- Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tübingen, Tübingen, Germany,
| | - Hoai-Nam Huynh
- Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Johanna Hebsaker
- Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Stephan Forchhammer
- Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Amir Sadegh Yazdi
- Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tübingen, Tübingen, Germany.,Department of Dermatology, RWTH Aachen, Aachen, Germany
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Román‐Carrasco P, Lieder B, Somoza V, Ponce M, Szépfalusi Z, Martin D, Hemmer W, Swoboda I. Only α-Gal bound to lipids, but not to proteins, is transported across enterocytes as an IgE-reactive molecule that can induce effector cell activation. Allergy 2019; 74:1956-1968. [PMID: 31102539 PMCID: PMC6852507 DOI: 10.1111/all.13873] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 04/09/2019] [Accepted: 04/18/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND The oligosaccharide galactose-α-1,3-galactose (α-Gal), present in mammalian proteins and lipids, causes an unusual delayed allergic reaction 3 to 6 hours after ingestion of mammalian meat in individuals with IgE antibodies against α-Gal. To better understand the delayed onset of allergic symptoms and investigate whether protein-bound or lipid-bound α-Gal causes these symptoms, we analyzed the capacity of α-Gal conjugated proteins and lipids to cross a monolayer of intestinal cells. METHODS Extracts of proteins and lipids from beef were prepared, subjected to in vitro digestions, and added to Caco-2 cells grown on permeable supports. The presence of α-Gal in the basolateral medium was investigated by immunoblotting, thin-layer chromatography with immunostaining and ELISA, and its allergenic activity was analyzed in a basophil activation test. RESULTS After addition of beef proteins to the apical side of Caco-2 cells, α-Gal containing peptides were not detected in the basolateral medium. Those peptides that crossed the Caco-2 monolayer did not activate basophils from an α-Gal allergic patient. Instead, when Caco-2 cells were incubated with lipids extracted from beef, α-Gal was detected in the basolateral medium. Furthermore, these α-Gal lipids were able to activate the basophils of an α-Gal allergic patient in a dose-dependent manner. CONCLUSION Only α-Gal bound to lipids, but not to proteins, is able to cross the intestinal monolayer and trigger an allergic reaction. This suggests that the slower digestion and absorption of lipids might be responsible for the unusual delayed allergic reactions in α-Gal allergic patients and identifies glycolipids as potential allergenic molecules.
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Affiliation(s)
| | - Barbara Lieder
- Department of Physiological Chemistry, Faculty of Chemistry University of Vienna Vienna Austria
| | - Veronika Somoza
- Department of Physiological Chemistry, Faculty of Chemistry University of Vienna Vienna Austria
| | - Marta Ponce
- Department of Pediatrics and Adolescent Medicine Medical University of Vienna Vienna Austria
| | - Zsolt Szépfalusi
- Department of Pediatrics and Adolescent Medicine Medical University of Vienna Vienna Austria
| | - Diana Martin
- Departamento de Producción y Caracterización de Nuevos Alimentos Instituto de Investigación en Ciencias de la Alimentación (CIAL) (CSIC‐UAM) Madrid Spain
| | | | - Ines Swoboda
- Molecular Biotechnology Section University of Applied Sciences Vienna Austria
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Raheem D, Raposo A, Oluwole OB, Nieuwland M, Saraiva A, Carrascosa C. Entomophagy: Nutritional, ecological, safety and legislation aspects. Food Res Int 2019; 126:108672. [PMID: 31732082 DOI: 10.1016/j.foodres.2019.108672] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 09/02/2019] [Accepted: 09/09/2019] [Indexed: 12/27/2022]
Abstract
Globally, there is a need to seek alternative sources of protein in addition to meat. This has led to considerable interest in edible insects. Such insects form part of cultures and diets in many Asian and African countries, and are an excellent source of essential nutrients, minerals, vitamins and proteins. Furthermore, they have been reported to be sustainable. The ecological importance of insects is related to their short life cycles when reared and farmed. This makes them ideal in mitigating greenhouse gas emissions, cutting land uses and polluted water, and reducing environmental contamination. However, the use of edible insects as food in Europe is minimal. To ensure safety of insects when eaten as food, considerations should be made on: microbiological contamination; toxicological hazards, e.g. chemical hazards and antinutrients; allergenicity issues that are related to different exposures, including injection, ingestion, inhalation and skin contact. In this review, we summarize the nutritional and sustainable values of edible insects, look at safety and legislative measures and we finally discuss future issues.
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Affiliation(s)
- Dele Raheem
- Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Viet Nam; Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Viet Nam.
| | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal.
| | | | - Maaike Nieuwland
- Food & Biobased Research, Wageningen University, Bornse Weilanden 9, 6708 WG Wageningen, The Netherlands
| | - Ariana Saraiva
- Pharmacy Faculty, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
| | - Conrado Carrascosa
- Department of Animal Pathology and Production, Bromatology and Food Technology, Faculty of Veterinary, Universidad de Las Palmas de Gran Canaria, Trasmontaña s/n, 35413 Arucas, Spain
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Abstract
Immunoglobulin E (IgE), though constitutively present at low levels, is most commonly studied in atopic disease where it plays a vital role in mast cell degranulation and in initiating a T helper 2 (Th2) response. With the advent of better detection assays, however, researchers are discovering the importance of IgE in actively contributing to many disease states and pathologies. This review will discuss the latest findings in IgE beyond its role in allergies and recently discovered roles for IgE in its cell-bound form on FcεRI-expressing effector cells like monocytes and dendritic cells. In terms of parasites, we will discuss helminth-induced IgE that appears to protect the worms from immune recognition and a tick-borne illness that elicits an IgE response against red meat. Next, we describe recent findings of how auto-reactive IgE can contribute to the progression of lupus and induce organ damage. Finally, we summarize the emerging roles of IgE in tumor surveillance and antibody-dependent cytotoxicity. We additionally discuss recent or ongoing clinical trials that either target harmful IgE or use the unique characteristics of the isotype.
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Affiliation(s)
- Andrea J Luker
- Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA
| | - Joseph C Lownik
- Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA.,Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA
| | - Daniel H Conrad
- Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA
| | - Rebecca K Martin
- Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA
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46
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Crispell G, Commins SP, Archer-Hartman SA, Choudhary S, Dharmarajan G, Azadi P, Karim S. Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy. Front Immunol 2019; 10:1056. [PMID: 31156631 PMCID: PMC6533943 DOI: 10.3389/fimmu.2019.01056] [Citation(s) in RCA: 113] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 04/24/2019] [Indexed: 01/01/2023] Open
Abstract
Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis. Anti-α-gal antibodies identified α-gal in the salivary glands of both Am. americanum and Ix. scapularis, while Am. maculatum and De. variabilis appeared to lack the carbohydrate. PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands. Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks. Am. americanum ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal. N-linked glycan analysis revealed that Am. americanum and Ix. scapularis have α-gal in their saliva and salivary glands, but Am. maculatum contains no detectable quantity. Consistent with the glycan analysis, salivary samples from Am. americanum and Ix. scapularis stimulated activation of basophils primed with plasma from α-gal allergic subjects. Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans. Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.
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Affiliation(s)
- Gary Crispell
- Department of Cell and Molecular Biology, School of Biological, Environment, and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
| | - Scott P Commins
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | | | - Shailesh Choudhary
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | - Guha Dharmarajan
- Savannah River Ecology Laboratory, University of Georgia, Aiken, SC, United States
| | - Parastoo Azadi
- Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States
| | - Shahid Karim
- Department of Cell and Molecular Biology, School of Biological, Environment, and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
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Pisazka V, Duscher G, Hodžić A, Reider N, Allerberger F. Alpha-gal allergy after a tick bite in Austria. Wien Klin Wochenschr 2019; 131:385-388. [PMID: 31087152 PMCID: PMC6702184 DOI: 10.1007/s00508-019-1506-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 04/26/2019] [Indexed: 11/20/2022]
Abstract
Tick bites can cause the alpha-gal syndrome, which is characterized by delayed anaphylactic reactions mainly to red meat and offal due to IgE antibodies against mammalian galactose-alpha-1.3-galactose carbohydrate (alpha-gal). Ixodes ricinus bites are considered the primary cause of IgE antibody responses specific for alpha-gal in Europe. This article reports on a 51-year-old Austrian male who acquired a tick bite in Austria in spring 2017, which, within 48 h, resulted in prolonged inflammation of the skin area around the bite. The patient experienced an allergic reaction 3 months later approximately 8 h after eating a medium rare steak for dinner. The symptoms included an itchy rash on both sides of the torso and on both arms which persisted for several hours. In spring 2018, the patient suffered another tick bite. The patient’s skin reaction was similar to that of the previous year. In the following months, the patient experienced five episodes of severe allergic reactions, each during the night after having eaten beef for dinner. The symptoms included pruritic urticarial rash involving the entire body along with swollen hands, diarrhea, vomiting and in some episodes even shortness of breath. At the request of the patient, specific IgE antibodies against alpha-gal were determined, revealing a highly positive result (>100 kU/l). This brief report aims to raise awareness that recurrent delayed anaphylactic reactions to food can develop after tick bites.
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Affiliation(s)
- Veronika Pisazka
- Austrian Agency for Health and Food Safety (AGES), Spargelfeldstraße 191, 1220, Vienna, Austria
| | - Georg Duscher
- Institute of Parasitology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Adnan Hodžić
- Institute of Parasitology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Norbert Reider
- Department of Dermatology, Venereology and Allergy, Medical University Innsbruck, Innsbruck, Austria
| | - Franz Allerberger
- Austrian Agency for Health and Food Safety (AGES), Spargelfeldstraße 191, 1220, Vienna, Austria.
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Mabelane T, Ogunbanjo GA. Ingestion of mammalian meat and alpha-gal allergy: Clinical relevance in primary care. Afr J Prim Health Care Fam Med 2019; 11:e1-e5. [PMID: 31038347 PMCID: PMC6494999 DOI: 10.4102/phcfm.v11i1.1901] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 11/16/2018] [Accepted: 11/21/2018] [Indexed: 11/05/2022] Open
Abstract
Background An allergic reaction to mammalian meat has recently been reported in rural parts of South Africa and throughout other parts of the world. The cause of this allergic reaction is because of an oligosaccharide antigen known as galactose-alpha-1, 3-galactose (alpha-gal) found in mammalian meat. Hard ticks in various parts of the world have been identified as a cause of sensitisation to the alpha-gal antigen. However, mechanisms of sensitisation in Africa are poorly understood. Aim The aim of this article is to review current literature on the alpha-gal allergy and mammalian meat ingestion and the family physician’s role in diagnosing and managing this condition. Method Indexes were searched using the keywords in the following electronic databases: Elsevier Science Direct, Google Scholar, Medline and PubMed. Results Clinical presentation of the alpha-gal allergy occurs typically as a delayed anaphylaxis occurring within 3–6 hours after the ingestion of mammalian meat. A subset of patients described in South Africa presented with a rapid onset of symptoms occurring within 45 minutes. Furthermore, some of these patients present with abdominal symptoms only, which may be mistaken as food poisoning. Diagnosis is based on a history of reaction to mammalian meats (especially to fatty portions or organs) and serum specific alpha-gal antibodies. The main management of the alpha-gal allergy is avoidance of red meat and in mild reactions treatment with oral H1 receptor antihistamines. Conclusion Sensitisation to the alpha-gal allergy results in adverse reactions to red meat, with tolerance to turkey, chicken and fish. A family physician can safely manage this condition. Keywords alpha-gal allergy; mammalian meat; management; primary care; specific IgE antibody; alpha-gal sensitisation.
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49
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Rentzos G, Johanson L, Goksör E, Telemo E, Lundbäck B, Ekerljung L. Prevalence of food hypersensitivity in relation to IgE sensitisation to common food allergens among the general adult population in West Sweden. Clin Transl Allergy 2019; 9:22. [PMID: 30976385 PMCID: PMC6442429 DOI: 10.1186/s13601-019-0261-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 03/18/2019] [Indexed: 11/10/2022] Open
Abstract
Background The prevalence of self-experienced adverse reactions to foods seems to have an increasing trend in both adults and children. However, it is unclear if the prevalence of food hypersensitivity in the Swedish adult population is still rising, what symptoms are caused by different foods and which are the most common foods to which adults are more frequently IgE-sensitised. Methods In a cross-sectional study based on questionnaire responses, interviews and clinical examinations as part of the West Sweden Asthma Study, 1042 subjects from the general population, 17–78 years of age, living in Västra Götaland, Sweden, were included. The subjects reported symptoms for 56 specified foods and blood samples were taken to examine the IgE-sensitisation pattern for 9 common foods. Results Approximately 32% of adults reported food hypersensitivity, affecting mostly women and subjects less than 61 years old. The foods most often reported to cause adverse reactions were hazelnut (8.9%), apple (8.4%), milk (7.4%) and kiwi (7.3%). Less than one percent (0.9%) reported symptoms from ingestion of meat. Symptoms mostly affected the gastrointestinal tract (15%) and the skin (2.7%). Sixteen per cent were IgE-sensitised to common foods, most often to hazelnut (13.3%), peanut (4.9%) and almond (3.0%), while 5.9% reported symptoms and were IgE-sensitised to the same food, mainly to hazelnut (5.3%). Conclusions The prevalence of self-reported food hypersensitivity in West Sweden indicates a rising trend. The correspondence between self-reported symptoms and IgE-sensitisation to foods is generally poor, except for hazelnut and almond which exhibit moderate or fair correlation.
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Affiliation(s)
- G Rentzos
- 1Krefting Research Centre, Institution for Medicine, Sahlgrenska Academy, University of Gothenburg, P.O Box 424, 405 30 Gothenburg, Sweden
| | - L Johanson
- 2Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Emma Goksör
- 3Department of Pediatrics, University of Gothenburg, Queen Silvia Children's Hospital, Gothenburg, Sweden
| | - E Telemo
- 4Deptartment for Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Bo Lundbäck
- 2Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - L Ekerljung
- 2Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Saretta F, Mori F, Cardinale F, Liotti L, Franceschini F, Crisafulli G, Caimmi S, Bottau P, Bernardini R, Caffarelli C. Pediatric drug hypersensitivity: which diagnostic tests? ACTA BIO-MEDICA : ATENEI PARMENSIS 2019; 90:94-107. [PMID: 30830067 PMCID: PMC6502170 DOI: 10.23750/abm.v90i3-s.8171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 02/01/2019] [Indexed: 12/14/2022]
Abstract
Along with the anamnesis and clinical evaluation, diagnostic tests are one of the mainstream key points in the evaluation and management of drug hypersensitivity reactions (DHR). A wide knowledge gap, both in diagnosis and management of pediatric DHR, must be filled. Only a few published studies evaluated sensitivity and specificity of skin and in vitro tests in children. However, selected case series show that diagnostic work-up for adults could be useful, with some limitations, in pediatric age. Indeed, despite improvement in in vivo and in vitro diagnosis, drug provocation test remains the gold standard in pediatric age, too. Unmet needs in children include multi-centric studies on incidence of DHR, utility and feasibility of in vivo and in vitro diagnostic tests and specifically dedicated guidelines for the diagnosis and management of DHR in children.
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Affiliation(s)
- Francesca Saretta
- Pediatric Department, AAS2 Bassa Friulana-Isontina, Palmanova-Latisana, Italy; Pediatric Allergy Unit, Department of Medicine, Udine, Italy.
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