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Balla J, Rathore APS, St. John AL. Maternal IgE Influence on Fetal and Infant Health. Immunol Rev 2025; 331:e70029. [PMID: 40281548 PMCID: PMC12032057 DOI: 10.1111/imr.70029] [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: 03/24/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025]
Abstract
Immunoglobulin E (IgE) is the most recently discovered and evolved mammalian antibody type, best known for interacting with mast cells (MCs) as immune effectors. IgE-mediated antigen sensing by MC provides protection from parasites, venomous animals, bacteria, and other insults to barrier tissues exposed to the environment. IgE and MCs act as inflammation amplifiers and immune response adjuvants. Thus, IgE production and memory formation are greatly constrained and require specific licensing. Failure of regulation gives rise to allergic disease, one of the top causes of chronic illness. Increasing evidence suggests allergy development often starts early in life, including prenatally, with maternal influence being central in shaping the offspring's immune system. Although IgE often exists before birth, an endogenous source of IgE-producing B cells has not been identified. This review discusses the mechanisms of maternal IgE transfer into the offspring, its interactions with offspring MCs and antigen-presenting cells, and the consequences for allergic inflammation and allergen sensitization development. We discuss the multifaceted effects of pre-existing IgG, IgE, and their glycosylation on maternal IgE transfer and functionality in the progeny. Understanding the IgE-mediated mechanisms predisposing for early life allergy development may allow their targeting with existing therapeutics and guide the development of new ones.
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Affiliation(s)
- Jozef Balla
- Programme in Emerging Infectious DiseasesDuke‐National University of Singapore Medical SchoolSingaporeSingapore
| | - Abhay P. S. Rathore
- Programme in Emerging Infectious DiseasesDuke‐National University of Singapore Medical SchoolSingaporeSingapore
- Department of PathologyDuke University Medical CenterDurhamNorth CarolinaUSA
| | - Ashley L. St. John
- Programme in Emerging Infectious DiseasesDuke‐National University of Singapore Medical SchoolSingaporeSingapore
- Department of PathologyDuke University Medical CenterDurhamNorth CarolinaUSA
- Department of Microbiology and Immunology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
- SingHealth Duke‐NUS Global Health InstituteSingaporeSingapore
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Jin Y, Boss AP, Bursley JK, Wilson C, Gangur V, Rockwell CE. The transcription factor Nrf2 links Th2-mediated experimental allergy to food preservatives. Front Immunol 2025; 15:1476480. [PMID: 40115160 PMCID: PMC11922944 DOI: 10.3389/fimmu.2024.1476480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 12/23/2024] [Indexed: 03/23/2025] Open
Abstract
Introduction Immune-mediated adverse reactions to food allergens are rising at a striking rate, for reasons that are not completely understood. Our previous studies suggest that the stress-activated transcription factor Nrf2 (Nuclear factor erythroid 2 -related factor) promotes Th2 differentiation, while inhibiting Th1 differentiation. Methods In the present studies, we investigated the effect of Nrf2 activation on sensitization and anaphylaxis in response to food allergen in BALB/c mice. Specifically, we determined the effect of the Nrf2 activator and common food preservative tBHQ (tert-butylhydroquinone) on immune response to food allergen in Balb/c mice and SCID mice that received either wild-type or Nrf2-deficient CD4 T cells. Results Our results demonstrate that tBHQ strongly increases IgE sensitization to ovalbumin (OVA) with a concurrent increase in plasma IgG1 concentrations. In addition, tBHQ in diet also exacerbated anaphylaxis and increased mast cell degranulation. In a recall response, tBHQ promoted a type 2 T cell response. Notably, adoptive transfer studies in SCID recipient mice indicate that Nrf2 expression in CD4+ T cells is critical to sensitization and anaphylaxis in response to food allergen. Likewise, the effects of tBHQ on sensitization and challenge are dependent on Nrf2 expression in CD4+ T cells. Conclusion Overall, these studies point to a key role for Nrf2 in the immune response to food allergen. In addition, this study shows that the common food preservative tBHQ promotes allergic sensitization and anaphylaxis in experimental food allergy.
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Affiliation(s)
- Yining Jin
- Department of Pharmacology and Toxicology, College of Human Medicine Michigan State University, East Lansing, MI, United States
| | - Allison P. Boss
- Department of Pharmacology and Toxicology, College of Human Medicine Michigan State University, East Lansing, MI, United States
- Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
| | - Jenna K. Bursley
- Department of Pharmacology and Toxicology, College of Human Medicine Michigan State University, East Lansing, MI, United States
| | - Caitlin Wilson
- Department of Pharmacology and Toxicology, College of Human Medicine Michigan State University, East Lansing, MI, United States
| | - Venugopal Gangur
- Food Allergy & Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States
| | - Cheryl E. Rockwell
- Department of Pharmacology and Toxicology, College of Human Medicine Michigan State University, East Lansing, MI, United States
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Loke P, Wang X, Lloyd M, Ashley SE, Lozinsky AC, Gold M, O'Sullivan MD, Quinn P, Robinson M, Galvin AD, Orsini F, Tang MLK. Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study. Allergy 2024; 79:2759-2774. [PMID: 39099231 DOI: 10.1111/all.16262] [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: 12/19/2023] [Revised: 06/15/2024] [Accepted: 07/08/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission). METHODS Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic). RESULTS 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001). CONCLUSION By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcome over desensitization or remaining allergic.
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Affiliation(s)
- Paxton Loke
- Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
- Monash Children's Hospital, Monash Health, Clayton, Victoria, Australia
| | - Xiaofang Wang
- Murdoch Children's Research Institute, Parkville, Victoria, Australia
| | - Melanie Lloyd
- Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Centre for Medicine Use and Safety, Monash University, Parkville, Victoria, Australia
| | - Sarah E Ashley
- Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
- Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Victoria, Australia
| | | | - Michael Gold
- Department of Paediatrics, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Women's and Children's Hospital Adelaide, North Adelaide, South Australia, Australia
| | - Michael D O'Sullivan
- Immunology Department, Perth Children's Hospital, Child and Adolescent Health Service, Nedlands, Western Australia, Australia
- Discipline of Paediatrics, Medical School, The University of Western Australia, Perth, Western Australia, Australia
- Telethon Kids Institute, Nedlands, Western Australia, Australia
| | - Patrick Quinn
- Department of Paediatrics, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Women's and Children's Hospital Adelaide, North Adelaide, South Australia, Australia
| | - Marnie Robinson
- Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Victoria, Australia
| | - Audrey Dunn Galvin
- School of Applied Psychology, Cork University Hospital, University College Cork, Cork, Ireland
- Allergy Research Network, Ireland
| | - Francesca Orsini
- Murdoch Children's Research Institute, Parkville, Victoria, Australia
| | - Mimi L K Tang
- Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
- Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Victoria, Australia
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Nesovic LD, Gonzalez Cruz PE, Rychener N, Wilks LR, Gill HS. Standardizing the skin tape stripping method for sensitization and using it to create a mouse model of peanut allergy. Int J Pharm 2024; 662:124479. [PMID: 39019298 DOI: 10.1016/j.ijpharm.2024.124479] [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: 03/30/2024] [Revised: 07/11/2024] [Accepted: 07/14/2024] [Indexed: 07/19/2024]
Abstract
BACKGROUND Animal models for food allergies serve as crucial tools in understanding allergy mechanisms and assessing the efficacy of potential desensitization methods. The effectiveness of inducing allergies in mice through intragastric lavage sensitization varies. The intraperitoneal method can trigger systemic anaphylaxis, however it lacks anatomical relevance. Hence, a uniform and reliable allergy induction method in mice is required. Tape -stripping can mimic atopic dermatitis (AD), a precursor to lifelong peanut allergies in humans. Furthermore, skin damage triggers the upregulation of skin alarmins and the expansion of small-intestinal mast cells, both implicated in allergy development. METHODS We standardized a skin-based sensitization method in a mouse model of peanut allergy using skin tape-stripping followed by allergen application. We compared this method with intragastric sensitization. RESULTS Skin-based sensitization led to increased mast cells, goblet cells, and eosinophils in the small intestine, elevated systemic IgE levels, murine mast cell protease-1 (mMCP-1), histamine, and eosinophilic activity in peripheral blood. Moreover, it resulted in a significant hypothermic response, with nearly 30% mortality following an oral challenge one-month post-sensitization. CONCLUSION Our research offers a standardized and readily reproducible method for inducing peanut allergy in mice, which could also be adapted for other food allergens.
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Affiliation(s)
- Lazar D Nesovic
- Department of Chemical Engineering, Texas Tech University, 8th and Canton, Lubbock, TX 79409, USA
| | - Pedro E Gonzalez Cruz
- Department of Chemical Engineering, Texas Tech University, 8th and Canton, Lubbock, TX 79409, USA
| | - Natalie Rychener
- Department of Chemical Engineering, Texas Tech University, 8th and Canton, Lubbock, TX 79409, USA
| | - Logan R Wilks
- Department of Chemical Engineering, Texas Tech University, 8th and Canton, Lubbock, TX 79409, USA
| | - Harvinder S Gill
- Department of Chemical Engineering, Texas Tech University, 8th and Canton, Lubbock, TX 79409, USA; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695, USA.
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Matatia PR, Christian E, Sokol CL. Sensory sentinels: Neuroimmune detection and food allergy. Immunol Rev 2024; 326:83-101. [PMID: 39092839 PMCID: PMC11436315 DOI: 10.1111/imr.13375] [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] [Indexed: 08/04/2024]
Abstract
Food allergy is classically characterized by an inappropriate type-2 immune response to allergenic food antigens. However, how allergens are detected and how that detection leads to the initiation of allergic immunity is poorly understood. In addition to the gastrointestinal tract, the barrier epithelium of the skin may also act as a site of food allergen sensitization. These barrier epithelia are densely innervated by sensory neurons, which respond to diverse physical environmental stimuli. Recent findings suggest that sensory neurons can directly detect a broad array of immunogens, including allergens, triggering sensory responses and the release of neuropeptides that influence immune cell function. Reciprocally, immune mediators modulate the activation or responsiveness of sensory neurons, forming neuroimmune feedback loops that may impact allergic immune responses. By utilizing cutaneous allergen exposure as a model, this review explores the pivotal role of sensory neurons in allergen detection and their dynamic bidirectional communication with the immune system, which ultimately orchestrates the type-2 immune response. Furthermore, it sheds light on how peripheral signals are integrated within the central nervous system to coordinate hallmark features of allergic reactions. Drawing from this emerging evidence, we propose that atopy arises from a dysregulated neuroimmune circuit.
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Affiliation(s)
- Peri R. Matatia
- Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
- Department of Immunology, Harvard Medical School, Boston, MA, 02115, USA
| | - Elena Christian
- Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
- Department of Immunology, Harvard Medical School, Boston, MA, 02115, USA
| | - Caroline L. Sokol
- Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
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Krempski J, Yamani A, Thota LNR, Marella S, Ganesan V, Sharma A, Kaneshige A, Bai L, Zhou H, Foster PS, Wang S, Obi AT, Hogan SP. IL-4-STAT6 axis amplifies histamine-induced vascular endothelial dysfunction and hypovolemic shock. J Allergy Clin Immunol 2024; 154:719-734. [PMID: 38777155 DOI: 10.1016/j.jaci.2024.05.009] [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: 07/13/2023] [Revised: 04/22/2024] [Accepted: 05/02/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Mast cell-derived mediators induce vasodilatation and fluid extravasation, leading to cardiovascular failure in severe anaphylaxis. We previously revealed a synergistic interaction between the cytokine IL-4 and the mast cell-derived mediator histamine in modulating vascular endothelial (VE) dysfunction and severe anaphylaxis. The mechanism by which IL-4 exacerbates histamine-induced VE dysfunction and severe anaphylaxis is unknown. OBJECTIVE We sought to identify the IL-4-induced molecular processes regulating the amplification of histamine-induced VE barrier dysfunction and the severity of IgE-mediated anaphylactic reactions. METHODS RNA sequencing, Western blot, Ca2+ imaging, and barrier functional analyses were performed on the VE cell line (EA.hy926). Pharmacologic degraders (selective proteolysis-targeting chimera) and genetic (lentiviral short hairpin RNA) inhibitors were used to determine the roles of signal transducer and activator of transcription 3 (STAT3) and STAT6 in conjunction with in vivo model systems of histamine-induced hypovolemic shock. RESULTS IL-4 enhancement of histamine-induced VE barrier dysfunction was associated with increased VE-cadherin degradation, intracellular calcium flux, and phosphorylated Src levels and required transcription and de novo protein synthesis. RNA sequencing analyses of IL-4-stimulated VE cells identified dysregulation of genes involved in cell proliferation, cell development, and cell growth, and transcription factor motif analyses revealed a significant enrichment of differential expressed genes with putative STAT3 and STAT6 motif. IL-4 stimulation in EA.hy926 cells induced both serine residue 727 and tyrosine residue 705 phosphorylation of STAT3. Genetic and pharmacologic ablation of VE STAT3 activity revealed a role for STAT3 in basal VE barrier function; however, IL-4 enhancement and histamine-induced VE barrier dysfunction was predominantly STAT3 independent. In contrast, IL-4 enhancement and histamine-induced VE barrier dysfunction was STAT6 dependent. Consistent with this finding, pharmacologic knockdown of STAT6 abrogated IL-4-mediated amplification of histamine-induced hypovolemia. CONCLUSIONS These studies unveil a novel role of the IL-4/STAT6 signaling axis in the priming of VE cells predisposing to exacerbation of histamine-induced anaphylaxis.
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Affiliation(s)
- James Krempski
- Mary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich
| | - Amnah Yamani
- Mary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich; Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | | | - Sahiti Marella
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Mich
| | - Varsha Ganesan
- Mary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich; Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Mich
| | - Ankit Sharma
- Mary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich
| | - Atsunori Kaneshige
- Department of Internal Medicine, University of Michigan, Ann Arbor, Mich; Department of Pharmacology, University of Michigan, Ann Arbor, Mich; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Mich
| | - Longchuan Bai
- Department of Internal Medicine, University of Michigan, Ann Arbor, Mich; Department of Pharmacology, University of Michigan, Ann Arbor, Mich; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Mich
| | - Haibin Zhou
- Department of Internal Medicine, University of Michigan, Ann Arbor, Mich; Department of Pharmacology, University of Michigan, Ann Arbor, Mich; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Mich
| | - Paul S Foster
- School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, and Immune Health Program, Hunter Medical Research Institute, Newcastle, Australia
| | - Shaomeng Wang
- Department of Internal Medicine, University of Michigan, Ann Arbor, Mich; Department of Pharmacology, University of Michigan, Ann Arbor, Mich; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Mich
| | - Andrea T Obi
- Conrad Jobst Vascular Research Laboratories, University of Michigan Medical School, Ann Arbor, Mich
| | - Simon P Hogan
- Mary H. Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich; Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, Mich.
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Liu EG, Yin X, Siniscalco ER, Eisenbarth SC. Dendritic cells in food allergy, treatment, and tolerance. J Allergy Clin Immunol 2024; 154:511-522. [PMID: 38971539 PMCID: PMC11414995 DOI: 10.1016/j.jaci.2024.06.017] [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: 05/23/2024] [Accepted: 06/13/2024] [Indexed: 07/08/2024]
Abstract
Food allergy is a growing problem with limited treatment options. It is important to understand the mechanisms of food tolerance and allergy to promote the development of directed therapies. Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that prime adaptive immune responses, such as those involved in the development of oral tolerance and food allergies. The DC subsets in the gut and skin are defined by their surface markers and function. The default response to an ingested innocuous antigen is oral tolerance, which requires either gut DCs or a subset of newly identified RORγt+ APCs to induce the development of gut peripheral regulatory T cells. However, DCs in the skin, gut, and lung can also promote allergic sensitization when they are activated under certain inflammatory conditions, such as with alarmin release or gut dysbiosis. DCs also play a role in the responses to the various modalities of food immunotherapy. Langerhans cells in the skin appear to be necessary for the response to epicutaneous immunotherapy. It will be important to determine which real-world stimuli activate the DCs that prime allergic sensitization and discover methods to selectively initiate a tolerogenic program in APCs.
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Affiliation(s)
- Elise G Liu
- Section of Rheumatology, Allergy and Immunology, Department of Medicine, Yale University School of Medicine, New Haven, Conn
| | - Xiangyun Yin
- Department of Immunobiology, Yale University School of Medicine, New Haven, Conn
| | - Emily R Siniscalco
- Department of Immunobiology, Yale University School of Medicine, New Haven, Conn; Center for Human Immunobiology, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Stephanie C Eisenbarth
- Department of Immunobiology, Yale University School of Medicine, New Haven, Conn; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Center for Human Immunobiology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
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Risemberg EL, Smeekens JM, Cruz Cisneros MC, Hampton BK, Hock P, Linnertz CL, Miller DR, Orgel K, Shaw GD, de Villena FPM, Burks AW, Valdar W, Kulis MD, Ferris MT. A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice. J Allergy Clin Immunol 2024; 154:387-397. [PMID: 38670234 PMCID: PMC11323216 DOI: 10.1016/j.jaci.2024.03.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 03/12/2024] [Accepted: 03/22/2024] [Indexed: 04/28/2024]
Abstract
BACKGROUND The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice. OBJECTIVE This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice. METHODS A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 mice and 5 additional Collaborative Cross strains. RESULTS Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis and 4% having severe anaphylaxis. There were 8 genetic loci associated with variation in response to peanut challenge-6 associated with anaphylaxis (temperature decrease) and 2 associated with peanut-specific IgE levels. There were 2 major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis gene. Consistent with described functions of Themis, we found that CC027 mice have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127- regulatory T cells. CONCLUSIONS Our results demonstrate a key role for Themis in the orally reactive CC027 mouse model of peanut allergy.
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Affiliation(s)
- Ellen L Risemberg
- Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Johanna M Smeekens
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Marta C Cruz Cisneros
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Brea K Hampton
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Pablo Hock
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Colton L Linnertz
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Darla R Miller
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Kelly Orgel
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Ginger D Shaw
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Fernando Pardo Manuel de Villena
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - A Wesley Burks
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - William Valdar
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
| | - Michael D Kulis
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
| | - Martin T Ferris
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
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Anagnostou A, Yaworsky A, Brova M, Ibrahim N, Kakked S, Spite S, Duluc L, Shields AL, Lee T, Leonard S, Przywara K, Smith A. Evaluation and Modification of a Shared Decision-Making Tool for Peanut Allergy Management. Curr Allergy Asthma Rep 2024; 24:303-315. [PMID: 38639896 DOI: 10.1007/s11882-024-01146-w] [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: 04/02/2024] [Indexed: 04/20/2024]
Abstract
PURPOSE OF REVIEW Based on shared decision-making (SDM) principles, a decision aid was previously developed to help patients, their caregivers, and physicians decide which peanut allergy management approach best suits them. This study refined the decision aid's content to better reflect patients' and caregivers' lived experience. RECENT FINDINGS Current standard of care for peanut allergy is avoidance, although peanut oral immunotherapy has been approved by the Food and Drug Administration for use in patients 4-17 years old. An advisory board of allergy therapy experts (n = 3) and patient advocates (n = 3) informed modifications to the decision aid. The revised tool underwent cognitive debriefing interviews (CDIs) among adolescents (12-17 years old) with peanut allergy and caregivers of patients 4-17 years old with peanut allergy to evaluate its relevance, understandability, and usefulness. The 20 CDI participants understood the information presented in the SDM tool and reported it was important and relevant. Some revisions were made based on participant feedback. Results support content validity of the Peanut Allergy Treatment SDM Tool.
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Affiliation(s)
| | - Andrew Yaworsky
- Adelphi Values, One Lincoln Street, Suite 2400, Boston, MA, 02111, USA.
| | - Monica Brova
- Adelphi Values, One Lincoln Street, Suite 2400, Boston, MA, 02111, USA
| | - Nazifa Ibrahim
- Adelphi Values, One Lincoln Street, Suite 2400, Boston, MA, 02111, USA
| | - Siddharth Kakked
- Adelphi Values, One Lincoln Street, Suite 2400, Boston, MA, 02111, USA
| | - Sasha Spite
- California State University San Marcos, San Marcos, CA, USA
| | - Linette Duluc
- Adelphi Values, One Lincoln Street, Suite 2400, Boston, MA, 02111, USA
| | - Alan L Shields
- Adelphi Values, One Lincoln Street, Suite 2400, Boston, MA, 02111, USA
| | - Tricia Lee
- Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA, USA
- American College of Allergy, Asthma, and Immunology, Arlington Heights, IL, USA
| | - Stephanie Leonard
- University of California San Diego, San Diego, CA, USA
- Rady Children's Hospital, San Diego, CA, USA
| | - Kathy Przywara
- Asthma and Allergy Foundation of America, Arlington, VA, USA
| | - Amelia Smith
- Food Allergy and Anaphylaxis Connection Team, Liberty Twp, OH, USA
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Połomska J, Dydak P, Sozańska B, Sikorska-Szaflik H. Peanut Allergy and Component-Resolved Diagnostics Possibilities-What Are the Benefits? Nutrients 2023; 15:5132. [PMID: 38140391 PMCID: PMC10746123 DOI: 10.3390/nu15245132] [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: 10/30/2023] [Revised: 12/05/2023] [Accepted: 12/13/2023] [Indexed: 12/24/2023] Open
Abstract
Peanut allergy is a widespread and potentially life-threatening condition that affects both children and adults, with a growing incidence worldwide. It is estimated to affect around 1-2% of the population in several developed countries. Component-resolved diagnostics is a modern approach to allergy diagnosis that focuses on identifying specific allergenic proteins to provide precise diagnoses and personalized treatment plans. It is a technique that enables the analysis of specific IgE antibodies against tightly defined molecules (components) that constitute the allergen. Component-resolved diagnostics is particularly valuable in peanut allergy diagnosis, helping to determine allergen components associated with severe reactions. It also aids in predicting the course of the allergy and enables the development of personalized immunotherapy plans; however, the full application of it for these purposes still requires more precise studies. In this paper, we present the current knowledge about peanut allergy and component-resolved diagnostics possibilities. We discuss the possibilities of using molecular diagnostics in the diagnosis of peanut allergy. We focus on examining and predicting the development of peanut allergy, including the risk of anaphylaxis, and describe the latest data related to desensitization to peanuts.
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Affiliation(s)
- Joanna Połomska
- Department and Clinic of Paediatrics, Allergology and Cardiology, Wroclaw Medical University, ul. Chałubińskiego 2a, 50-368 Wrocław, Poland; (J.P.); (B.S.)
| | - Paulina Dydak
- Clinical Department of Paediatrics, Specialist Hospital No. 2, Bytom, Silesian Medical University, 40-055 Katowice, Poland;
| | - Barbara Sozańska
- Department and Clinic of Paediatrics, Allergology and Cardiology, Wroclaw Medical University, ul. Chałubińskiego 2a, 50-368 Wrocław, Poland; (J.P.); (B.S.)
| | - Hanna Sikorska-Szaflik
- Department and Clinic of Paediatrics, Allergology and Cardiology, Wroclaw Medical University, ul. Chałubińskiego 2a, 50-368 Wrocław, Poland; (J.P.); (B.S.)
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11
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Shichkin VP, Kurchenko OV, Okhotnikova EN, Chopyak VV, Delfino DV. Enterosorbents in complex therapy of food allergies: a focus on digestive disorders and systemic toxicity in children. Front Immunol 2023; 14:1210481. [PMID: 37901242 PMCID: PMC10611465 DOI: 10.3389/fimmu.2023.1210481] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 10/03/2023] [Indexed: 10/31/2023] Open
Abstract
The review analyzes mechanisms and concomitant factors in developing IgE-associated allergic diseases provoked by food allergens and discusses clinical symptoms and current approaches for the treatment of food allergies. The expediency of using enterosorbents in complex therapy of food allergies and skin and respiratory manifestations associated with gastroenterological disorders is substantiated. The review summarizes the experience of using enterosorbents in post-Soviet countries to detoxify the human body. In this regard, special attention is paid to the enterosorbent White Coal (Carbowhite) based on silicon dioxide produced by the Ukrainian company OmniFarma.
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Affiliation(s)
| | | | - Elena N. Okhotnikova
- Department of Pediatrics, Children’s Infectious Diseases, Immunology and Allergology, Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine
| | - Valentyna V. Chopyak
- Department of Clinical Immunology and Allergology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Domenico V. Delfino
- Master in Musculoskeletal and Rheumatological Physiotherapy, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
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12
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Zhao Y, He W, Zhao S, Jiao T, Hu H, Li J, Zhang L, Zang J. Advanced Insights into Walnut Protein: Structure, Physiochemical Properties and Applications. Foods 2023; 12:3603. [PMID: 37835256 PMCID: PMC10572233 DOI: 10.3390/foods12193603] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/18/2023] [Accepted: 09/21/2023] [Indexed: 10/15/2023] Open
Abstract
Facing extreme pressure from an increasing population and climate degeneration, it is important to explore a green, safe and environmentally sustainable food source, especially for protein-enriched diets. Plant proteins have gained much attention in recent years, ascribing to their high nutritional value and environmental friendliness. In this review, we summarized recent advances in walnut protein with respect to its geographical distribution, structural and physiochemical properties and functional attributes. As a worldwide cultivated and largely consumptive crop, allergies and some physicochemical limitations have also led to a few concerns about walnut protein. Through comprehensive analysis and discussion, some strategies may be useful for future research, extraction and processing of walnut protein.
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Affiliation(s)
- Yuxuan Zhao
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.Z.); (W.H.); (S.Z.)
| | - Weiheng He
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.Z.); (W.H.); (S.Z.)
| | - Sihan Zhao
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.Z.); (W.H.); (S.Z.)
| | - Teng Jiao
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.Z.); (W.H.); (S.Z.)
| | - Haifang Hu
- Academy of Forestry Sciences, Urumqi 830062, China
| | - Jingming Li
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.Z.); (W.H.); (S.Z.)
| | - Lei Zhang
- College of Forestry and Landscape Architecture, Xinjiang Agricultural University, Urumqi 830052, China
| | - Jiachen Zang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.Z.); (W.H.); (S.Z.)
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13
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Smeekens JM, Immormino RM, Kesselring JR, Turner AV, Kulis MD, Moran TP. A single priming event prevents oral tolerance to peanut. Clin Exp Allergy 2023; 53:930-940. [PMID: 37437951 PMCID: PMC10528191 DOI: 10.1111/cea.14373] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 06/02/2023] [Accepted: 06/28/2023] [Indexed: 07/14/2023]
Abstract
BACKGROUND Indoor dust (ID) is a source of peanut proteins and immunostimulatory adjuvants (e.g. LPS) that can promote airway sensitization to peanut. We aimed to determine whether a single airway exposure to peanut plus adjuvant is sufficient to prevent oral tolerance. METHODS To determine the effect of a single priming event, C57BL/6J mice were exposed once to peanut plus adjuvant through the airway, followed by either airway or low-dose oral exposure to peanut, and assessed for peanut allergy. Oral tolerance was investigated by feeding high-dose peanut followed by airway sensitization. To determine whether a single priming could prevent oral tolerance, the high-dose peanut regimen was applied after a single airway exposure to peanut plus adjuvant. Peanut-specific IgE and IgG1 were quantified, and mice were challenged to peanut to assess allergy. Peanut-specific CD4+ memory T cells (CD4+ TCRβ+ CD44hi CD154+ ) were quantified in mediastinal lymph nodes following airway priming. RESULTS Mice co-exposed to peanut with LPS or ID through the airway were primed to develop peanut allergy after subsequent low-dose oral or airway exposures to peanut. Oral tolerance was induced in mice fed high-dose peanut prior to airway sensitization. In contrast, mice fed high-dose peanut following a single airway exposure to peanut plus adjuvant led to allergy. Peanut-specific CD4+ memory T cells were detected as early as 7 days after the single airway priming with peanut plus adjuvant, however, delaying peanut feeding even 1 day following priming led to allergy, whereas peanut feeding the same day as priming led to tolerance. CONCLUSIONS A single airway exposure to peanut plus adjuvant is sufficient to prime the immune system to develop allergy following subsequent high-dose oral exposure. These results highlight the importance of introducing peanut as early as possible to prevent sensitization through a non-oral priming event.
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Affiliation(s)
- Johanna M Smeekens
- Department of Pediatrics, UNC School of Medicine, Chapel Hill, North Carolina, USA
- Department of Pediatrics, UNC Food Allergy Initiative, UNC School of Medicine, Chapel Hill, North Carolina, USA
| | - Robert M Immormino
- Department of Pediatrics, UNC School of Medicine, Chapel Hill, North Carolina, USA
| | - Janelle R Kesselring
- Department of Pediatrics, UNC School of Medicine, Chapel Hill, North Carolina, USA
- Department of Pediatrics, UNC Food Allergy Initiative, UNC School of Medicine, Chapel Hill, North Carolina, USA
| | - Andrew V Turner
- Department of Pediatrics, UNC School of Medicine, Chapel Hill, North Carolina, USA
- Department of Pediatrics, UNC Food Allergy Initiative, UNC School of Medicine, Chapel Hill, North Carolina, USA
| | - Michael D Kulis
- Department of Pediatrics, UNC School of Medicine, Chapel Hill, North Carolina, USA
- Department of Pediatrics, UNC Food Allergy Initiative, UNC School of Medicine, Chapel Hill, North Carolina, USA
| | - Timothy P Moran
- Department of Pediatrics, UNC School of Medicine, Chapel Hill, North Carolina, USA
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14
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Turner AV, Smeekens JM. Environmental Exposure to Foods as a Risk Factor for Food Allergy. Curr Allergy Asthma Rep 2023; 23:427-433. [PMID: 37227666 DOI: 10.1007/s11882-023-01091-0] [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: 05/06/2023] [Indexed: 05/26/2023]
Abstract
PURPOSE OF REVIEW Many factors have been reported to contribute to the development of food allergy. Here, we summarize the role of environmental exposure to foods as a major risk factor for developing food allergy. RECENT FINDINGS Peanut proteins are detectable and biologically active in household environments, where infants spend a majority of their time, providing an environmental source of allergen exposure. Recent evidence from clinical studies and mouse models suggests both the airway and skin are routes of exposure that lead to peanut sensitization. Environmental exposure to peanut has been clearly associated with the development of peanut allergy, although other factors such as genetic predisposition, microbial exposures, and timing of oral feeding of allergens also likely contribute. Future studies should more comprehensively assess the contributions of each of these factors for a variety of food allergens to provide more clear targets for prevention of food allergy.
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Affiliation(s)
- Andrew V Turner
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina at Chapel Hill, 116 Manning Dr., Mary Ellen Jones, Room 3310, Chapel Hill, NC, 27599, USA
| | - Johanna M Smeekens
- Division of Allergy and Immunology, Department of Pediatrics, University of North Carolina at Chapel Hill, 116 Manning Dr., Mary Ellen Jones, Room 3310, Chapel Hill, NC, 27599, USA.
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15
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Sharma A, Rijavec M, Tomar S, Yamani A, Ganesan V, Krempski J, Schuler CF, Bunyavanich S, Korosec P, Hogan SP. Acute systemic myeloid inflammatory and stress response in severe food allergic reactions. Clin Exp Allergy 2023; 53:536-549. [PMID: 36756745 PMCID: PMC11157667 DOI: 10.1111/cea.14273] [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: 08/19/2022] [Revised: 10/28/2022] [Accepted: 11/20/2022] [Indexed: 02/10/2023]
Abstract
INTRODUCTION Food allergic reactions can be severe and potentially life-threatening and the underlying immunological processes that contribute to the severity of reactions are poorly understood. The aim of this study is to integrate bulk RNA-sequencing of human and mouse peripheral blood mononuclear cells during food allergic reactions and in vivo mouse models of food allergy to identify dysregulated immunological processes associated with severe food allergic reactions. METHODS Bulk transcriptomics of whole blood from human and mouse following food allergic reactions combined with integrative differential expressed gene bivariate and module eigengene network analyses to identify the whole blood transcriptome associated with food allergy severity. In vivo validation immune cell and gene expression in mice following IgE-mediated reaction. RESULTS Bulk transcriptomics of whole blood from mice with different severity of food allergy identified gene ontology (GO) biological processes associated with innate and inflammatory immune responses, dysregulation of MAPK and NFkB signalling and identified 429 genes that correlated with reaction severity. Utilizing two independent human cohorts, we identified 335 genes that correlated with severity of peanut-induced food allergic reactions. Mapping mouse food allergy severity transcriptome onto the human transcriptome revealed 11 genes significantly dysregulated and correlated with severity. Analyses of whole blood from mice undergoing an IgE-mediated reaction revealed a rapid change in blood leukocytes particularly inflammatory monocytes (Ly6Chi Ly6G- ) and neutrophils that was associated with changes in CLEC4E, CD218A and GPR27 surface expression. CONCLUSIONS Collectively, IgE-mediated food allergy severity is associated with a rapid innate inflammatory response associated with acute cellular stress processes and dysregulation of peripheral blood inflammatory myeloid cell frequencies.
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Affiliation(s)
- Ankit Sharma
- Mary H Weiser Food Allergy Center, Department of Pathology, Michigan Medicine, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
| | - Matija Rijavec
- University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia
- Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Sunil Tomar
- Mary H Weiser Food Allergy Center, Department of Pathology, Michigan Medicine, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
| | - Amnah Yamani
- Mary H Weiser Food Allergy Center, Department of Pathology, Michigan Medicine, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Varsha Ganesan
- Mary H Weiser Food Allergy Center, Department of Pathology, Michigan Medicine, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
| | - James Krempski
- Mary H Weiser Food Allergy Center, Department of Pathology, Michigan Medicine, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
| | - Charles F Schuler
- Mary H Weiser Food Allergy Center, Department of Pathology, Michigan Medicine, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
- Division of Allergy and Immunology, Michigan medicine University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
| | - Supinda Bunyavanich
- Division of Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY; Icahn Institute for Data Science and Genome Technology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Peter Korosec
- University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia
- Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Simon P. Hogan
- Mary H Weiser Food Allergy Center, Department of Pathology, Michigan Medicine, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
- Department of Pathology, Michigan Medicine, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200
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Bedolla-Barajas M, Morales-Romero J, Sánchez-Magallón R, Valdez-Soto JA, Bedolla-Pulido TR, Meza-López C. Food allergy among Mexican infants and preschoolers: prevalence and associated factors. World J Pediatr 2023; 19:401-405. [PMID: 36520272 DOI: 10.1007/s12519-022-00649-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 11/01/2022] [Indexed: 12/16/2022]
Affiliation(s)
- Martín Bedolla-Barajas
- Allergy and Immunology Department, Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Salvador Quevedo y Zubieta No. 740, Colonia La Perla, 44340, Guadalajara, Jalisco, México.
| | | | - Rafael Sánchez-Magallón
- Allergy and Immunology Department, Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Salvador Quevedo y Zubieta No. 740, Colonia La Perla, 44340, Guadalajara, Jalisco, México
| | - Jorge Alejandro Valdez-Soto
- Allergy and Immunology Department, Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Salvador Quevedo y Zubieta No. 740, Colonia La Perla, 44340, Guadalajara, Jalisco, México
| | | | - Carlos Meza-López
- Pediatrics Department, Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Guadalajara, Mexico
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17
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Giannetti A, Ruggi A, Ricci G, Giannì G, Caffarelli C. Natural History of Hazelnut Allergy and Current Approach to Its Diagnosis and Treatment. CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10030585. [PMID: 36980143 PMCID: PMC10047188 DOI: 10.3390/children10030585] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/13/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023]
Abstract
Hazelnut allergy is the most prevalent type of nut allergy in Europe, with symptoms that can range from mild, such as hives and itching, to severe, such as anaphylaxis, particularly in patients who are sensitized to highly stable allergens, such as storage proteins. Compared to other types of food allergies, allergies to tree nuts, including hazelnuts, tend to persist throughout life. Although symptoms can appear in early childhood, they often continue into adulthood, with a minority of cases improving during adolescence. Currently, there is no curative treatment available for hazelnut allergy, and patients must adhere to a restrictive diet and carry autoinjective epinephrine. However, oral allergen immunotherapy (AIT) is a promising treatment option. Patients can be categorized based on their risk for severe reactions using various clinical, in vivo, and in vitro tests, including component-resolved diagnosis and oral food challenge. This review aims to provide an overview of the current knowledge of the natural history of hazelnut allergy and new approaches for its diagnosis and management.
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Affiliation(s)
- Arianna Giannetti
- Paediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Alessandro Ruggi
- Specialty School of Pediatrics, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Giampaolo Ricci
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy
| | - Giuliana Giannì
- Clinica Pediatrica, Azienda Ospedaliero-Universitaria, Medicine and Surgery Department, Università di Parma, 43126 Parma, Italy
| | - Carlo Caffarelli
- Clinica Pediatrica, Azienda Ospedaliero-Universitaria, Medicine and Surgery Department, Università di Parma, 43126 Parma, Italy
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18
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Grzeskowiak LE, Tao B, Aliakbari K, Chegeni N, Morris S, Chataway T. Oral immunotherapy using boiled peanuts for treating peanut allergy: An open-label, single-arm trial. Clin Exp Allergy 2023; 53:327-336. [PMID: 36628520 DOI: 10.1111/cea.14254] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/21/2022] [Accepted: 10/27/2022] [Indexed: 01/12/2023]
Abstract
BACKGROUND Peanut allergy affects 1%-3% of children in Western countries. Boiling peanuts has been demonstrated to result in a hypoallergenic product that may provide a safer way of inducing desensitization in peanut-allergic patients by first inducing tolerance to boiled peanut. We aimed to assess the efficacy and safety of oral immunotherapy (OIT) using sequential doses of boiled peanuts followed by roasted peanuts for treating peanut allergy in children. METHODS In this open-label, phase 2, single-arm clinical trial, children aged 6-18 years with a positive history of peanut allergy and positive peanut skin prick test ≥ 8 mm and/or peanut-specific IgE ≥ 15 kU/L at screening underwent OIT involving sequential up-dosing with 12-hour boiled peanut for 12 weeks, 2-hour boiled peanut for 20 weeks and roasted peanut for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily. PRIMARY OUTCOME proportion of children passing open-label oral food challenge involving cumulative administration of 12 roasted peanuts (12 g peanuts; approximately 3000 mg peanut protein) 6-8 weeks after reaching the target maintenance dose. Secondary outcomes included treatment-related adverse events and use of medications for treating allergy symptoms. RESULTS Between 1 July 2017 and 22 June 2018, 70 participants were enrolled and commenced OIT. Desensitization was successfully induced in 56 of 70 (80%) participants. Withdrawal due to treatment-related adverse events was infrequent (n = 3). Treatment-related adverse events were reported in 43 (61%) participants, corresponding to a rate of 6.58 per 1000 OIT doses. Medication use associated with treatment-related adverse events was infrequent, with rescue epinephrine use reported by three (4%) participants (0.05 per 1000 doses). CONCLUSION Oral immunotherapy using boiled followed by roasted peanuts represents a pragmatic approach that appears effective in inducing desensitization and is associated with a favourable safety profile.
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Affiliation(s)
- Luke E Grzeskowiak
- Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Billy Tao
- Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Allergy SA, Adelaide, South Australia, Australia
| | - Kamelya Aliakbari
- Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Nusha Chegeni
- Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Scott Morris
- Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Department of Neonatal-Perinatal Medicine, Flinders Medical Centre, SA Health, Adelaide, South Australia, Australia
| | - Tim Chataway
- Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
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Palladino C, Ellinger I, Kalic T, Humeniuk P, Ret D, Mayr V, Hafner C, Hemmer W, Hoffmann-Sommergruber K, Untersmayr E, Bublin M, Radauer C, Breiteneder H. Peanut lipids influence the response of bronchial epithelial cells to the peanut allergens Ara h 1 and Ara h 2 by decreasing barrier permeability. Front Mol Biosci 2023; 10:1126008. [PMID: 36845549 PMCID: PMC9945344 DOI: 10.3389/fmolb.2023.1126008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 01/26/2023] [Indexed: 02/11/2023] Open
Abstract
Background: Peanut-allergic individuals react upon their first known ingestion of peanuts, suggesting sensitization occurs through non-oral exposure. Increasing evidence suggests that the respiratory tract is a probable site for sensitization to environmental peanuts. However, the response of the bronchial epithelium to peanut allergens has never been explored. Furthermore, food matrix-derived lipids play an important role in allergic sensitization. Objective: To contribute to a better understanding of the mechanisms of allergic sensitization to peanuts via inhalation, by exploring the direct effect of the major peanut allergens Ara h 1 and Ara h 2 and peanut lipids on bronchial epithelial cells. Methods: Polarized monolayers of the bronchial epithelial cell line 16HBE14o- were stimulated apically with peanut allergens and/or peanut lipids (PNL). Barrier integrity, transport of allergens across the monolayers, and release of mediators were monitored. Results: Ara h 1 and Ara h 2 impacted the barrier integrity of the 16HBE14o- bronchial epithelial cells and crossed the epithelial barrier. Ara h 1 also induced the release of pro-inflammatory mediators. PNL improved the barrier function of the cell monolayers, decreased paracellular permeability and reduced the amount of allergens crossing the epithelial layer. Conclusion: Our study provides evidence of the transport of Ara h 1 and Ara h 2 across the airway epithelium, of the induction of a pro-inflammatory milieu, and identifies an important role for PNL in controlling the amount of allergens that can cross the epithelial barrier. These, all together, contribute to a better understanding of the effects of peanuts exposure on the respiratory tract.
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Affiliation(s)
- Chiara Palladino
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Isabella Ellinger
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Tanja Kalic
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Department of Dermatology, University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria
| | - Piotr Humeniuk
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Davide Ret
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Division of Macromolecular Chemistry, Institute of Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria
| | - Vanessa Mayr
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Christine Hafner
- Department of Dermatology, University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria
- Karl Landsteiner Institute for Dermatological Research, St. Pölten, Austria
| | | | - Karin Hoffmann-Sommergruber
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Eva Untersmayr
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Merima Bublin
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Christian Radauer
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Heimo Breiteneder
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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20
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Koczoń P, Hołaj-Krzak JT, Palani BK, Bolewski T, Dąbrowski J, Bartyzel BJ, Gruczyńska-Sękowska E. The Analytical Possibilities of FT-IR Spectroscopy Powered by Vibrating Molecules. Int J Mol Sci 2023; 24:ijms24021013. [PMID: 36674526 PMCID: PMC9860999 DOI: 10.3390/ijms24021013] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 12/30/2022] [Accepted: 01/01/2023] [Indexed: 01/06/2023] Open
Abstract
This paper discusses the state of advancement in the development of spectroscopic methods based on the use of mid (proper) infrared radiation in the context of applications in various fields of science and technology. The authors drew attention to the most important solutions specific to both spectroscopy itself (ATR technique) and chemometric data processing tools (PCA and PLS models). The objective of the current paper is to collect and consistently present information on various aspects of FT-IR spectroscopy, which is not only a well-known and well-established method but is also continuously developing. The innovative aspect of the current review is to show FT-IR's great versatility that allows its applications to solve and explain issues from both the scientific domain (e.g., hydrogen bonds) and practical ones (e.g., technological processes, medicine, environmental protection, and food analysis). Particular attention was paid to the issue of hydrogen bonds as key non-covalent interactions, conditioning the existence of living matter and determining the number of physicochemical properties of various materials. Since the role of FT-IR spectroscopy in the field of hydrogen bond research has great significance, a historical outline of the most important qualitative and quantitative hydrogen bond theories is provided. In addition, research on selected unconventional spectral effects resulting from the substitution of protons with deuterons in hydrogen bridges is presented. The state-of-the-art and originality of the current review are that it presents a combination of uses of FT-IR spectroscopy to explain the way molecules vibrate and the effects of those vibrations on macroscopic properties, hence practical applications of given substances.
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Affiliation(s)
- Piotr Koczoń
- Department of Chemistry, Institute of Food Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland
| | - Jakub T. Hołaj-Krzak
- Institute of Technology and Life Sciences—National Research Institute, 3 Hrabska Ave., Falenty, 05-090 Raszyn, Poland
| | - Bharani K. Palani
- Department of Chemistry, Institute of Food Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland
| | - Tymoteusz Bolewski
- Institute of Technology and Life Sciences—National Research Institute, 3 Hrabska Ave., Falenty, 05-090 Raszyn, Poland
| | - Jarosław Dąbrowski
- Institute of Technology and Life Sciences—National Research Institute, 3 Hrabska Ave., Falenty, 05-090 Raszyn, Poland
| | - Bartłomiej J. Bartyzel
- Department of Morphological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-776 Warsaw, Poland
| | - Eliza Gruczyńska-Sękowska
- Department of Chemistry, Institute of Food Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland
- Correspondence:
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Kazmi W, Berin MC. Oral tolerance and oral immunotherapy for food allergy: Evidence for common mechanisms? Cell Immunol 2023; 383:104650. [PMID: 36543052 DOI: 10.1016/j.cellimm.2022.104650] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/21/2022] [Accepted: 11/26/2022] [Indexed: 12/05/2022]
Abstract
Food allergies affect up to 10% of the US population, can be life-threatening, and have a significant negative impact on quality of life. Delayed dietary introduction of foods in childhood can hinder the induction of oral tolerance, an active regulatory response to foods that prevents the development of food allergy. Some children outgrow their food allergies naturally, while many others have persistent, lifelong food allergy for which there are few therapeutic options. Oral immunotherapy (OIT) is a therapeutic approach of giving increasing amounts of food to attempt to desensitize the allergic individual. In this review, we focus on the immune mechanisms common to oral tolerance and response to oral immunotherapy, with the objective of determining whether true tolerance can be achieved after food allergy has been established.
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Affiliation(s)
- Wajiha Kazmi
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - M Cecilia Berin
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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22
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Lee AJ, Tham EH, Goh AEN, Tang WE, Tung YC, Yeo Y, Tsou K, Lee LY, Soh JY, Labastida CB, Wang PP, Tan MML, Cheng HY, Chan YH, Van Bever H, Shek LPC, Lee BW. Prevalence of IgE-mediated cow milk, egg, and peanut allergy in young Singapore children. Asia Pac Allergy 2022; 12:e31. [PMID: 35966156 PMCID: PMC9353200 DOI: 10.5415/apallergy.2022.12.e31] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/11/2022] [Indexed: 12/31/2022] Open
Abstract
Background The rising prevalence of food allergy reported in the United States, UK, and Australia may be attributable to the rise in peanut allergy prevalence. The food allergy prevalence in other parts of the world such as Asia is, however, less well documented. Objective This study aimed to evaluate the prevalence of cow's milk, egg, and peanut allergies in a general population of Singaporean children below 30 months of age. Methods A total of 4,115 children from the general population who attended well-baby visits between 2011 and 2015 completed standardized questionnaires to elicit a convincing history of food allergy to estimate the population prevalence of food allergies. Results The prevalence of a convincing history of cow's milk allergy was 0.51% (95% confidence interval [CI], 0.3-0.7), hen's egg allergy 1.43% (95% CI, 1.1-1.8), and peanut allergy 0.27% (95% CI, 0.12-0.42). Of the 15 of 59 children with a convincing history of hen's egg allergy who consented, 12 (80%) had corroborative positive skin prick tests. Conclusion The prevalence of food allergy, in particular peanut allergy, in children below 2 years of age is lower in this South East Asian population than reported in Western cohorts. Further research should focus on deciphering differential risk factors for food allergy across different geographical locations.
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Affiliation(s)
- Alison Joanne Lee
- Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, Singapore
| | - Elizabeth Huiwen Tham
- Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, Singapore
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Anne Eng-Neo Goh
- Department of Paediatrics, KKH Women’s and Children’s Hospital, Singapore
| | - Wern-Ee Tang
- National Healthcare Group of Polyclinics (NHGP), Singapore
| | | | - Yehudi Yeo
- National Healthcare Group of Polyclinics (NHGP), Singapore
| | - Keith Tsou
- National University Polyclinics, Singapore
| | - Le-Ye Lee
- Department of Neonatology, National University Hospital, Singapore
| | - Jian-Yi Soh
- Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, Singapore
| | - Cesar Brence Labastida
- Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, Singapore
| | - Ping-Ping Wang
- Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, Singapore
| | - Michelle Mei-Ling Tan
- Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, Singapore
| | - Hsin Yue Cheng
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yiong-Huak Chan
- Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Hugo Van Bever
- Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, Singapore
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Lynette Pei-Chi Shek
- Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, Singapore
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Bee-Wah Lee
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Labrosse R, Graham F, Caubet JC. Recent advances in the diagnosis and management of tree nut and seed allergy. Curr Opin Allergy Clin Immunol 2022; 22:194-201. [DOI: 10.1097/aci.0000000000000826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Mishra A, Majid D, Kandikattu HK, Yadavalli CS, Upparahalli Venkateshaiah S. Role of IL-18-transformed CD274-expressing eosinophils in promoting airway obstruction in experimental asthma. Allergy 2022; 77:1165-1179. [PMID: 34800294 DOI: 10.1111/all.15180] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/30/2021] [Accepted: 10/18/2021] [Indexed: 01/21/2023]
Abstract
BACKGROUND IL-5-dependent residential and IL-18-transformed pathogenic eosinophils have been reported; however, the role of IL-18-transformed CD274-expressing pathogenic eosinophils compared to IL-5-generated eosinophils in promoting airway obstruction in asthma has not yet been examined. METHODS Eosinophils are detected by tissue anti-MBP and anti-EPX immunostaining, CD274 expression by flow cytometry, and airway resistance using the Buxco FinePointe RC system. RESULTS We show that A. fumigatus-challenged wild-type mice, and different gene-deficient mice including naïve CC10-IL-18-transgenic mice, accumulate mostly peribronchial and perivascular CD274-expressing eosinophils except naïve CD2-IL-5-transgenic mice. Additionally, we show that CD2-IL-5 transgenic mice following rIL-18 treatment accumulate high number of CD274-expressing perivascular and peribronchial eosinophils with induced collagen, goblet cell hyperplasia and airway resistance compared to saline-challenged CD2-IL5 transgenic mice. Furthermore, we also show that even A. fumigatus-challenged IL-5 -/- mice and rIL-18 given ΔdblGATA mice accumulate CD274-expressing eosinophil-associated asthma pathogenesis including airway obstruction. Most importantly, we provide evidence that neutralization of CD274 and IL-18 in A. fumigatus-challenged mice ameliorate experimental asthma. Taken together, the data presented are clinically significant in establishing that anti-IL-18 neutralization is a novel immunotherapy to restrict asthma pathogenesis. CONCLUSIONS We demonstrate that IL-18 is critical for inducing asthma pathogenesis, and neutralization of CD274 is a potential immunotherapeutic strategy for asthma.
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Affiliation(s)
- Anil Mishra
- John W. Deming Department of Medicine Tulane Eosinophilic Disorders Center (TEDC) Section of Pulmonary Diseases Tulane University School of Medicine New Orleans Louisina USA
| | - Dewan Majid
- John W. Deming Department of Medicine Tulane Eosinophilic Disorders Center (TEDC) Section of Pulmonary Diseases Tulane University School of Medicine New Orleans Louisina USA
| | - Hemanth Kumar Kandikattu
- John W. Deming Department of Medicine Tulane Eosinophilic Disorders Center (TEDC) Section of Pulmonary Diseases Tulane University School of Medicine New Orleans Louisina USA
| | - Chandra Sekhar Yadavalli
- John W. Deming Department of Medicine Tulane Eosinophilic Disorders Center (TEDC) Section of Pulmonary Diseases Tulane University School of Medicine New Orleans Louisina USA
| | - Sathisha Upparahalli Venkateshaiah
- John W. Deming Department of Medicine Tulane Eosinophilic Disorders Center (TEDC) Section of Pulmonary Diseases Tulane University School of Medicine New Orleans Louisina USA
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Soyak Aytekin E, Unsal H, Sahiner UM, Soyer O, Sekerel BE. IgE mediated legume allergy in east Mediterranean children: A reflection of multiple food allergies. Pediatr Allergy Immunol 2022; 33:e13775. [PMID: 35470935 DOI: 10.1111/pai.13775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 03/27/2022] [Accepted: 04/04/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Legumes are nutritionally valuable as an inexpensive protein source, but may cause severe allergic reactions. This study aimed to identify the characteristics of legume allergies (LAs) in Turkish children. METHODS A total of 87 children (4.9 (3.1-7.0) years) with LAs confirmed by either oral food challenge (OFC) or consistent history were reviewed. RESULTS The median age of onset was 19 (12-38) months. The most frequent LA was lentil (n = 57, 66%), followed by peanut (n = 53, 61%), chickpea (n = 24, 28%), pea (n = 21, 24%), bean (n = 7, 8%), and soybean (n = 1, 1%). From these, it was observed that 60% had multilegume (≥2) allergies and the age of onset occurred earlier compared with the single LA subgroup (18 (11-30) vs. 28 (17-42) months, p = .042). Single LA was present in peanut (51%) and lentil (16%) allergies, but not chickpea, pea, and bean. Fifteen patients had tolerated lentils before their first allergic reaction. The majority of children with LA (91.9%) were allergic to multiple foods including tree nuts (71%), hen's egg (66%), and cow's milk (49%). Seventy-eight patients (89.7%) also presented with atopic comorbidities concerning atopic dermatitis (70%), asthma (40%), and allergic rhinitis (30%). Patients with anaphylactic type of reaction (20%) had higher frequency of aeroallergen sensitization (p = .001). Lip dose challenge with legume paste predicted the result of OFC with a diagnostic accuracy of 81.82% and a positive likelihood ratio of 10.8. CONCLUSION In Turkey, LA is a reflection of multiple food allergies and the presence of allergy to a least frequently encountered legume is a sign of multiple LA.
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Affiliation(s)
- Elif Soyak Aytekin
- Department of Pediatric Allergy, Hacettepe University School of Medicine, Ankara, Turkey
| | - Hilal Unsal
- Department of Pediatric Allergy, Hacettepe University School of Medicine, Ankara, Turkey
| | - Umit Murat Sahiner
- Department of Pediatric Allergy, Hacettepe University School of Medicine, Ankara, Turkey
| | - Ozge Soyer
- Department of Pediatric Allergy, Hacettepe University School of Medicine, Ankara, Turkey
| | - Bulent Enis Sekerel
- Department of Pediatric Allergy, Hacettepe University School of Medicine, Ankara, Turkey
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Juel-Berg N, Larsen LF, Küchen N, Norgil I, Hansen KS, Poulsen LK. Patterns of Clinical Reactivity in a Danish Cohort of Tree Nut Allergic Children, Adolescents, and Young Adults. FRONTIERS IN ALLERGY 2022; 3:824660. [PMID: 35958942 PMCID: PMC9361471 DOI: 10.3389/falgy.2022.824660] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 02/24/2022] [Indexed: 11/13/2022] Open
Abstract
Background Tree nut allergy is associated with severe reactions and poly-sensitization to other nuts and peanuts often occurs. There are regional differences in sensitization profiles that result in differences in clinical presentation. Denmark is located in a birch pollen endemic area, which could influence the allergy patterns due to pollen cross-sensitization. Objective This study aimed to investigate patterns of sensitization and clinical reactivity to tree nuts and peanuts and threshold levels for oral food challenges (OFCs) in a Danish cohort of tree nut allergic children, adolescents, and young adults. Methods Forty tree nut allergic subjects were assessed for clinical reactivity to six nuts, i.e., hazelnut, walnut, pistachio, cashew, almond, and peanut, by OFCs or convincing medical history of an immediate allergic reaction or tolerance. Clinical presentation and allergen-specific immunoglobulin E (sIgE) levels together with eliciting dose and rescue medication in OFCs were furthermore assessed. Results Allergy to two or more tree nuts was observed in most cases. Hazelnut-walnut dual allergy was common but not exclusively observed as concomitant allergies. Allergy to cashew was coincided in all but one of the assessed subjects with pistachio allergy. Half of all assessed subjects were allergic to peanuts. Oral symptoms followed by a skin reaction were the most common symptomatology that lead to OFC cessation and subjects often presented with symptoms from two or more organ systems. OFC threshold levels were within the same range, but cashew was distinguished from other nuts by causing allergic symptoms at the lowest dose. Clinical reactivity and the allergy patterns were to some extent reflected by sIgE levels and by correlations in sIgE between the nuts. Conclusions In this Northern European cohort, subjects with clinically relevant tree nut allergy were generally allergic to two or more tree nuts and close to half of them also to peanuts. There were two distinct and independent allergic phenotypes; the majority of hazelnut allergic subjects were also allergic to walnut, and all but one subject with cashew allergy were dual allergic to pistachio. These findings are consistent with a strong sIgE correlation between hazelnut and walnut and a close to total sIgE correlation between cashew and pistachio.
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Affiliation(s)
- Nanna Juel-Berg
- Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital, Gentofte, Denmark
- Department of Pediatrics, Copenhagen University Hospital, Herlev, Denmark
| | - Lau Fabricius Larsen
- Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital, Gentofte, Denmark
| | - Niels Küchen
- Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital, Gentofte, Denmark
- Department of Pediatrics, Copenhagen University Hospital, Herlev, Denmark
| | - Ida Norgil
- Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital, Gentofte, Denmark
- Department of Pediatrics, Copenhagen University Hospital, Herlev, Denmark
| | - Kirsten Skamstrup Hansen
- Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital, Gentofte, Denmark
- Department of Pediatrics, Copenhagen University Hospital, Herlev, Denmark
| | - Lars K. Poulsen
- Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital, Gentofte, Denmark
- *Correspondence: Lars K. Poulsen
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Loke P, Orsini F, Lozinsky AC, Gold M, O'Sullivan MD, Quinn P, Lloyd M, Ashley SE, Pitkin S, Axelrad C, Metcalfe JR, Su EL, Tey D, Robinson MN, Allen KJ, Prescott SL, Galvin AD, Tang MLK. Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial. THE LANCET. CHILD & ADOLESCENT HEALTH 2022; 6:171-184. [PMID: 35123664 DOI: 10.1016/s2352-4642(22)00006-2] [Citation(s) in RCA: 76] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/22/2021] [Accepted: 12/23/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. METHODS PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437. FINDINGS Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% [95% CI 27·46 to 53·42] for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% [-20·40 to 10·34], p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 [95% CI 0·85 to 0·99] for PPOIT vs OIT, p=0·042; 4·98 [4·11-6·03] for PPOIT vs placebo, p<0·0001; 5·42 [4·48-6·56] for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two [3%] of 71 in the PPOIT group, four [6%] of 70 in the OIT group, and none in the placebo group). INTERPRETATION Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children. FUNDING National Health and Medical Research Council Australia and Prota Therapeutics.
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Affiliation(s)
- Paxton Loke
- Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, VIC, Australia; Monash Children's Hospital, Clayton, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
| | - Francesca Orsini
- Murdoch Children's Research Institute, Parkville, VIC, Australia
| | - Adriana C Lozinsky
- Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, VIC, Australia
| | - Michael Gold
- Department of Paediatrics, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia; Women's and Children's Hospital Adelaide, North Adelaide, SA, Australia
| | - Michael D O'Sullivan
- Immunology Department, Perth Children's Hospital, Child and Adolescent Health Service, Nedlands, WA, Australia; Discipline of Paediatrics, Medical School, The University of Western Australia, Perth, WA, Australia; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
| | - Patrick Quinn
- Department of Paediatrics, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia; Women's and Children's Hospital Adelaide, North Adelaide, SA, Australia
| | - Melanie Lloyd
- Murdoch Children's Research Institute, Parkville, VIC, Australia; School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia
| | - Sarah E Ashley
- Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
| | - Sigrid Pitkin
- Murdoch Children's Research Institute, Parkville, VIC, Australia; Monash Children's Hospital, Clayton, VIC, Australia
| | | | - Jessica R Metcalfe
- Immunology Department, Perth Children's Hospital, Child and Adolescent Health Service, Nedlands, WA, Australia; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
| | - Ee Lyn Su
- Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, VIC, Australia
| | - Dean Tey
- Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, VIC, Australia
| | - Marnie N Robinson
- Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, VIC, Australia
| | - Katrina J Allen
- Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
| | - Susan L Prescott
- Immunology Department, Perth Children's Hospital, Child and Adolescent Health Service, Nedlands, WA, Australia; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia; NOVA Institute for Health, Baltimore, MD, USA; Department of Family and Community Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Audrey Dunn Galvin
- School of Applied Psychology, Cork University Hospital, University College Cork, Cork, Ireland; Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Mimi L K Tang
- Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
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Alghamdi R, Alshaier R, Alotaibi A, Almutairi A, Alotaibi G, Faqeeh A, Almalki A, AbdulMajed H. Immunotherapy Effectiveness in Treating Peanut Hypersensitivity: A Systemic Review. Cureus 2022; 14:e21832. [PMID: 35291522 PMCID: PMC8896406 DOI: 10.7759/cureus.21832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2022] [Indexed: 11/05/2022] Open
Abstract
Peanut hypersensitivity is one of the top causes of food-related allergic responses and death in high-income countries. As a result, the goal of this study was to see if various forms of immunotherapies can help reduce the severity of peanut hypersensitivity reactions. From 2019 to 2021, a systematic search of PubMed, Web of Science, Wiley online library, and Science Direct was done. Peanut immunotherapy (PIT) clinical trials were considered. There were 19 trials with a total of 1565 participants. Twelve were on oral immunotherapy (OIT), two on sublingual immunotherapy (SLIT), two on subcutaneous immunotherapy (SCIT), two on epicutaneous immunotherapy (EPIT), and one was a comparison of SLIT and OIT. Desensitization was achieved by 74.3% of those who received OIT, 11% of those who received SLIT, 61% of those who received SCIT, and 49% of those who received EPIT. The majority of adverse events (AE) were mild to moderate. Those requiring epinephrine, on the other hand, were moderate to severe and were more common in the therapy groups. This systematic review showed that the current PIT regimens can accomplish desensitization regardless of the route of administration, with an acceptable safety profile.
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Lange L, Klimek L, Beyer K, Blümchen K, Novak N, Hamelmann E, Bauer A, Merk HF, Rabe U, Jung K, Schlenter WW, Ring J, Chaker AM, Wehrmann W, Becker S, Mülleneisen NK, Nemat K, Czech W, Wrede H, Brehler R, Fuchs T, Jakob T, Ankermann T, Schmidt SM, Gerstlauer M, Zuberbier T, Spindler T, Vogelberg C. White Paper Erdnussallergie - Teil 1: Epidemiologie, Burden of Disease, gesundheitsökonomische Aspekte. ALLERGO JOURNAL 2021. [DOI: 10.1007/s15007-021-4935-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Tagliati S, Barni S, Giovannini M, Liccioli G, Sarti L, Alicandro T, Paladini E, Perferi G, Azzari C, Novembre E, Mori F. Nut Allergy: Clinical and Allergological Features in Italian Children. Nutrients 2021; 13:4076. [PMID: 34836333 PMCID: PMC8623984 DOI: 10.3390/nu13114076] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 11/11/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Nut allergies are an increasingly frequent health issue in the pediatric population. Tree nuts (TN) and peanuts are the second cause of food anaphylaxis in Italy. Unfortunately, knowledge of the clinical characteristics of a TN allergy in Italian children is limited. Our study aimed to identify the clinical and allergological characteristics of Italian children with a nut allergy (TN and peanut). METHODS A retrospective observational analysis was performed on the clinical charts of children with a history of nut reaction referred to the allergy unit of the hospital from 2015 to 2019. The studied population was represented by children with a confirmed nut allergy based on positive prick by prick and/or serum-specific IgE to nut plus a positive nut oral food challenge. Demographic, clinical, and allergological features were studied and compared among different nuts. RESULTS In total, 318 clinical charts were reviewed. Nut allergy was confirmed in 113 patients. Most patients (85/113, 75%) had a familial history of allergy and/or a concomitant allergic disorder (77/113, 68%). Hazelnut and walnut were the more common culprit nuts observed in allergic children. Anaphylaxis was the first clinical manifestation of nut allergy in a high percentage of children (54/113, 48%). The mean age of the first nut reaction was statistically higher with pine nuts. Over 75% of children reported a single nut reaction. During the OFCs, the signs and symptoms involved mainly the gastrointestinal system (82/113, 73%) and resolved spontaneously in most cases. Severe reactions were not frequent (22/113, 19%). CONCLUSION To our knowledge, this is the first Italian study that provided a comprehensive characterization of children with a nut allergy. These results are important for clinicians treating children with a nut allergy.
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Affiliation(s)
- Sylvie Tagliati
- Pediatric Unit, Sant’Anna University Hospital of Ferrara, 44124 Ferrara, Italy;
| | - Simona Barni
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, 50139 Florence, Italy; (S.B.); (G.L.); (L.S.); (E.N.); (F.M.)
| | - Mattia Giovannini
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, 50139 Florence, Italy; (S.B.); (G.L.); (L.S.); (E.N.); (F.M.)
| | - Giulia Liccioli
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, 50139 Florence, Italy; (S.B.); (G.L.); (L.S.); (E.N.); (F.M.)
| | - Lucrezia Sarti
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, 50139 Florence, Italy; (S.B.); (G.L.); (L.S.); (E.N.); (F.M.)
| | - Tatiana Alicandro
- Division of Allergy and Clinical Immunology, Dermatology Unit, Surgical, Medical and Dental Department of Morphological Science Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy;
| | - Erika Paladini
- Pediatric Respiratory and Allergy Unit, Women’s and Children’s Health Department, University of Padua, 35128 Padua, Italy;
| | - Giancarlo Perferi
- Section of Pediatrics, Department of Health Sciences, University of Florence and Meyer Children’s Hospital, 50139 Florence, Italy; (G.P.); (C.A.)
| | - Chiara Azzari
- Section of Pediatrics, Department of Health Sciences, University of Florence and Meyer Children’s Hospital, 50139 Florence, Italy; (G.P.); (C.A.)
| | - Elio Novembre
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, 50139 Florence, Italy; (S.B.); (G.L.); (L.S.); (E.N.); (F.M.)
| | - Francesca Mori
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, 50139 Florence, Italy; (S.B.); (G.L.); (L.S.); (E.N.); (F.M.)
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Hicks A, Palmer C, Bauer M, Venter C. Accidental ingestions to known allergens by food allergic children and adolescents. Pediatr Allergy Immunol 2021; 32:1718-1729. [PMID: 34091961 DOI: 10.1111/pai.13573] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 04/27/2021] [Accepted: 05/31/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Accidental ingestions (AI) of food allergens in children compared with adolescents with food allergies are poorly characterized. It is suggested that AIs are higher in adolescents than children and that their reactions may be more severe, presumptively due, at least in part, to increased risk-taking behavior. We compared reported AIs in children versus adolescents. METHODS An online cross-sectional survey was distributed to parents of children with food allergies via Twitter, food allergy advocacy groups in the UK, South Africa, and Australia, and locally at Children's Hospital Colorado. RESULTS Of 558 respondents, 105 were parents of adolescents, and 453 had children <12 years. 73% (341) reported an AI since diagnosis, with 85% of adolescents having had an AI versus 70% of children (p = 0.0058). The annualized rate of AI was significantly lower in the adolescent population at 0.21 versus 0.53 in children (p = <0.0001). Although adolescents reported fewer severe reactions (2% vs. 16%, p = 0.0283), more adolescents required epinephrine administered by a medical professional for their most severe AI, (48% vs. 24%, p = 0.0378). Comparison of the two age groups is limited by the fact that many AIs in the adolescent group occurred prior to age 12. There was no significant difference between the groups as to where the food was consumed or the type of food. There was a significant difference in accidental ingestions in patients in all age groups with more than one reported food allergy; 78% of those with more than one food allergy reported a prior history of at least one accidental ingestion, compared with 59% in those with a single food allergy (p < 0.0001). Regional differences were also noted with respondents in the United States reporting 0.3 accidental ingestions a year, 0.4 in the UK, and 0.5 in other countries (p = 0.0455). The number of reactions was, on average, 27% lower (95% CI: 40, 11%) in the United States compared with the UK (p = 0.0019). CONCLUSION The number of severe reactions, and epinephrine need, differs in children compared with adolescents, although many of the reported reactions in both groups occurred before the age of 12. There were also regional differences with the United States reporting a lower number of AIs and less AIs per year than the other participating regions, as well as increased rates of AI in participants with more than one food allergy. Further characterization of the differences in AIs between children and adolescents, as well as between regions, is needed to assist with more patient-centered anticipatory guidance.
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Affiliation(s)
- Allison Hicks
- Department of Pediatrics, Section of Allergy and Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA.,Children's Hospital Colorado, Aurora, Colorado, USA
| | - Claire Palmer
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Maureen Bauer
- Department of Pediatrics, Section of Allergy and Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA.,Children's Hospital Colorado, Aurora, Colorado, USA
| | - Carina Venter
- Department of Pediatrics, Section of Allergy and Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA.,Children's Hospital Colorado, Aurora, Colorado, USA
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32
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Muraro A, Sublett JW, Haselkorn T, Nilsson C, Casale TB. Incidence of anaphylaxis and accidental peanut exposure: A systematic review. Clin Transl Allergy 2021; 11:e12064. [PMID: 34708943 PMCID: PMC8694181 DOI: 10.1002/clt2.12064] [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: 04/09/2021] [Revised: 07/14/2021] [Accepted: 08/28/2021] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Peanut allergy (PA), a common food allergy, is increasing in prevalence and is associated with high rates of anaphylaxis. Prevalence of food-related anaphylaxis is higher in children and adolescents than in adults, and the pediatric incidence is increasing. We conducted a systematic literature review and meta-analysis to determine the incidence of peanut-induced anaphylaxis in children and/or adolescents with PA. METHODS Literature searches were conducted using the PubMed database and through supplemental methods. Eligible articles for inclusion were peer-reviewed studies published in English that reported the incidence of anaphylaxis in pediatric PA using the 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network criteria, sample size, and follow-up duration. Incidence rates were calculated as person-years at risk or a crude incidence rate was calculated. Meta-analyses of pooled data were conducted using the I2 statistic as the measure of heterogeneity. RESULTS A total of 830 citations were screened; 8 met the study inclusion criteria and were selected for review. Pooled meta-analysis estimates of the incidence of (1) anaphylaxis among children/adolescents with food allergies, (2) anaphylaxis among children/adolescents with PA, and (3) accidental exposure to peanuts among children/adolescents with PA were 3.72 cases per 100 person-years (95% confidence interval [CI] = 2.35, 5.10), 2.74 cases per 100 person-years (95% CI = 1.42, 4.05), and 12.28 cases per 100 person-years (95% CI = 11.51, 13.05), respectively. CONCLUSIONS The risks of anaphylaxis among children with food allergies and those with PA contribute to the serious overall burden of PA and food allergy for children and their families.
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Affiliation(s)
- Antonella Muraro
- Department of Woman and Child Health, Food Allergy Referral Centre Veneto Region, Padua University Hospital, Padua, Italy
| | | | | | - Caroline Nilsson
- Clinical Science and Education, Karolinska Institutet, Sodersjukhuset, Sachs' Children and Youth Hospital, Stockholm, Sweden
| | - Thomas B Casale
- Food Allergy Research and Education (FARE), University of South Florida, Tampa, Florida, USA
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Lange L, Klimek L, Beyer K, Blümchen K, Novak N, Hamelmann E, Bauer A, Merk H, Rabe U, Jung K, Schlenter W, Ring J, Chaker A, Wehrmann W, Becker S, Mülleneisen N, Nemat K, Czech W, Wrede H, Brehler R, Fuchs T, Jakob T, Ankermann T, Schmidt SM, Gerstlauer M, Zuberbier T, Spindler T, Vogelberg C. White paper on peanut allergy - part 1: Epidemiology, burden of disease, health economic aspects. ACTA ACUST UNITED AC 2021; 30:261-269. [PMID: 34603938 PMCID: PMC8477625 DOI: 10.1007/s40629-021-00189-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 06/21/2021] [Indexed: 01/27/2023]
Abstract
Peanuts are Leguminosae, commonly known as the legume or pea family, and peanut allergy is among the most common food allergies and the most common cause of fatal food reactions and anaphylaxis. The prevalence of peanut allergy increased 3.5-fold over the past two decades reaching 1.4–2% in Europe and the United States. The reasons for this increase in prevalence are likely multifaceted. Sensitization via the skin appears to be associated with the development of peanut allergy and atopic eczema in infancy is associated with a high risk of developing peanut allergy. Until recently, the only possible management strategy for peanut allergy was strict allergen avoidance and emergency treatment including adrenaline auto-injector in cases of accidental exposure and reaction. This paper discusses the various factors that impact the risks of peanut allergy and the burden of self-management on peanut-allergic children and their caregivers.
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Affiliation(s)
- Lars Lange
- Department of Pediatrics, St. Marien-Hospital, GFO Clinics Bonn, Bonn, Germany
| | - Ludger Klimek
- Center for Rhinology and Allergology Wiesbaden, Wiesbaden, Germany
| | - Kirsten Beyer
- Department of Pediatrics m.S. Pneumology, Immunology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Katharina Blümchen
- Center of Pediatric and Adolescent Medicine, Focus on Allergology, Pneumology and Cystic Fibrosis, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt a. M., Germany
| | - Natalija Novak
- Clinic and Polyclinic for Dermatology and Allergology, University Hospital Bonn, Bonn, Germany
| | - Eckard Hamelmann
- Pediatric and Adolescent Medicine, Bethel Children's Center, OWL University Hospital of Bielefeld University, Bielefeld, Germany
| | - Andrea Bauer
- Clinic and Polyclinic for Dermatology, University AllergyCenter, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
| | - Hans Merk
- Department of Dermatology & Allergology, RWTH Aachen, Aachen, Germany
| | - Uta Rabe
- Clinic for Allergology, Johanniter-Krankenhaus im Fläming Treuenbrietzen GmbH, Treuenbrietzen, Germany
| | - Kirsten Jung
- Practice for Dermatology, Immunology and Allergology, Erfurt, Germany
| | | | | | - Adam Chaker
- Department of Otolaryngology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.,Center for Allergy and Environment (ZAUM), Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | | | - Sven Becker
- Department of Otolaryngology, University of Tübingen, Tübingen, Germany
| | | | - Katja Nemat
- Pediatric Pneumology/Allergology Practice, Kinderzentrum Dresden (Kid), Dresden, Germany
| | - Wolfgang Czech
- Practice and clinic for allergology/dermatology, Schwarzwald-Baar Klinikum, Villingen-Schwenningen, Germany
| | - Holger Wrede
- Practice and clinic for allergology/ear, nose and throat specialist, Herford, Germany
| | - Randolf Brehler
- Clinic for Skin Diseases, Outpatient Clinic for Allergology, Occupational Dermatology and Environmental Medicine, Münster University Hospital, Münster, Germany
| | - Thomas Fuchs
- Department of Dermatology, Venereology and Allergology, University Hospital, Georg-August-University, Göttingen, Germany
| | - Thilo Jakob
- rd Clinic for Dermatology and Allergology University Hospital Giessen, UKGM Justus Liebig University Giessen, Giessen, Germany
| | - Tobias Ankermann
- th Clinic for Pediatric and Adolescent Medicine, Pneumology, Allergology, Neonatology, Intensive Care Medicine, Infectiology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Sebastian M Schmidt
- th Center for Pediatric and Adolescent Medicine, Clinic and Polyclinic for Pediatric and Adolescent Medicine, Greifswald University Medical Center, Greifswald, Germany
| | - Michael Gerstlauer
- pediatric pneumologist/pediatric allergologist, II. clinic for children and adolescents, University Hospital Augsburg, Augsburg, Germany
| | - Torsten Zuberbier
- Clinic for Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Thomas Spindler
- Department of Pediatrics and Adolescent Medicine, Pediatric Pneumology, Allergology, Sports Medicine, Hochgebirgsklinik Davos, Davos-Wolfgang, Switzerland
| | - Christian Vogelberg
- TU Dresden/UKDD, Pediatric Department, University Hospital Dresden, Dresden, Germany.,Department of Pediatric Pneumology/Allergology, Clinic and Polyclinic for Pediatrics and Adolescent Medicine, University Hospital Carl Gustav Carus, Fetscher Street 74, 01307 Dresden, Germany
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Fuhrmann V, Huang HJ, Akarsu A, Shilovskiy I, Elisyutina O, Khaitov M, van Hage M, Linhart B, Focke-Tejkl M, Valenta R, Sekerel BE. From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack. Front Immunol 2021; 12:742732. [PMID: 34630424 PMCID: PMC8496898 DOI: 10.3389/fimmu.2021.742732] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 08/23/2021] [Indexed: 12/02/2022] Open
Abstract
Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.
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Affiliation(s)
- Verena Fuhrmann
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Huey-Jy Huang
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Aysegul Akarsu
- Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Igor Shilovskiy
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Olga Elisyutina
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Musa Khaitov
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - Marianne van Hage
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University, Hospital, Stockholm, Sweden
| | - Birgit Linhart
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Margarete Focke-Tejkl
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Karl Landsteiner University of Health Sciences, Krems, Austria
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Bulent Enis Sekerel
- Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
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Loke P, Chebar Lozinsky A, Orsini F, Wong LSY, Leung ASY, Tham EH, Lopata AL, Shek LPC, Tang ML. Study protocol of a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg oral immunotherapy at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo (Probiotic Egg Allergen Oral Immunotherapy for Treatment of Egg Allergy: PEAT study). BMJ Open 2021; 11:e044331. [PMID: 34233966 PMCID: PMC8264865 DOI: 10.1136/bmjopen-2020-044331] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
INTRODUCTION Egg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo. METHODS AND ANALYSIS 80 participants aged 5-30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms-probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group. ETHICS AND DISSEMINATION This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. TRIAL REGISTRATION NUMBER ACTRN12619000480189.
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Affiliation(s)
- Paxton Loke
- Allergy Immunology, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia
- Monash Children's Hospital, Clayton, Victoria, Australia
| | | | - Francesca Orsini
- Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Melbourne Children's Trials Centre, Murdoch Children's Research Institute, Parkville, Victoria, Australia
| | - Lydia Su-Yin Wong
- Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore
| | - Agnes Sze-Yin Leung
- Allergy Immunology, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Elizabeth Huiwen Tham
- Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore
- Department of Paediatrics, National University Singapore Yong Loo Lin School of Medicine, Singapore
| | - Andreas L Lopata
- Molecular Allergy Research Laboratory, James Cook University College of Public Health Medical and Veterinary Sciences, Townsville, Queensland, Australia
| | - Lynette Pei-Chi Shek
- Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore
- Department of Paediatrics, National University Singapore Yong Loo Lin School of Medicine, Singapore
| | - Mimi Lk Tang
- Allergy Immunology, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia
- Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Victoria, Australia
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Anagnostou A. Addressing Common Misconceptions in Food Allergy: A Review. CHILDREN-BASEL 2021; 8:children8060497. [PMID: 34207962 PMCID: PMC8230601 DOI: 10.3390/children8060497] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/04/2021] [Accepted: 06/08/2021] [Indexed: 12/15/2022]
Abstract
Background: Food allergies are common, affecting 1 in 13 school children in the United States and their prevalence is increasing. Many misconceptions exist with regards to food allergy prevention, diagnosis and management. Objective: The main objective of this review is to address misconceptions with regards to food allergies and discuss the optimal, evidence-based approach for patients who carry this diagnosis. Observations: Common misconceptions in terms of food allergy prevention include beliefs that breastfeeding and delayed introduction of allergenic foods prevent the development of food allergies. In terms of diagnosis, statements such as ‘larger skin prick tests or/and higher levels of food-specific IgE can predict the severity of food-induced allergic reactions’, or ‘Tryptase is always elevated in food-induced anaphylaxis’ are inaccurate. Additionally, egg allergy is not a contraindication for receiving the influenza vaccine, food-allergy related fatalities are rare and peanut oral immunotherapy, despite reported benefits, is not a cure for food allergies. Finally, not all infants with eczema will develop food allergies and epinephrine auto-injectors may unfortunately be both unavailable and underused in food-triggered anaphylaxis. Conclusions and relevance: Healthcare professionals must be familiar with recent evidence in the food allergy field and avoid common misunderstandings that may negatively affect prevention, diagnosis and management of this chronic disease.
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Affiliation(s)
- Aikaterini Anagnostou
- Section of Immunology, Allergy and Retrovirology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; ; Tel.: +1-832-824-1319; Fax: +1-832-825-1260
- Section of Immunology, Allergy and Retrovirology, Department of Pediatrics, Texas Children’s Hospital, Houston, TX 77030, USA
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Lieberman JA, Gupta RS, Knibb RC, Haselkorn T, Tilles S, Mack DP, Pouessel G. The global burden of illness of peanut allergy: A comprehensive literature review. Allergy 2021; 76:1367-1384. [PMID: 33216994 PMCID: PMC8247890 DOI: 10.1111/all.14666] [Citation(s) in RCA: 98] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 10/30/2020] [Accepted: 11/14/2020] [Indexed: 01/05/2023]
Abstract
Peanut allergy (PA) currently affects approximately 2% of the general population of Western nations and may be increasing in prevalence. Patients with PA and their families/caregivers bear a considerable burden of self‐management to avoid accidental peanut exposure and to administer emergency medication (adrenaline) if needed. Compared with other food allergies, PA is associated with higher rates of accidental exposure, severe reactions and potentially fatal anaphylaxis. Approximately 7%–14% of patients with PA experience accidental peanut exposure annually, and one‐third to one‐half may experience anaphylaxis, although fatalities are rare. These risks impose considerably high healthcare utilization and economic costs for patients with PA and restrictions on daily activities. Measures to accommodate patients with PA are often inadequate, with inconsistent standards for food labelling and inadequate safety policies in public establishments such as restaurants and schools. Children with PA are often bullied, resulting in sadness, humiliation and anxiety. These factors cumulatively contribute to significantly reduced health‐related quality of life for patients with PA and families/caregivers. Such factors also provide essential context for risk/benefit assessments of new PA therapies. This narrative review comprehensively assessed the various factors comprising the burden of PA.
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Affiliation(s)
- Jay A. Lieberman
- University of Tennessee Health Science Center/Le Bonheur Children’s Hospital Memphis TN USA
| | - Ruchi S Gupta
- Institute for Public Health and Medicine Ann & Robert H. Lurie Children's Hospital of ChicagoNorthwestern School of Medicine Chicago IL USA
| | | | | | | | - Douglas P. Mack
- Department of Pediatrics McMaster University Hamilton ON Canada
| | - Guillaume Pouessel
- Pneumology and Allergology Unit Children's HospitalLille University Hospital Jeanne de Flandre France
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Warren C, Lei D, Sicherer S, Schleimer R, Gupta R. Prevalence and characteristics of peanut allergy in US adults. J Allergy Clin Immunol 2021; 147:2263-2270.e5. [PMID: 33579526 DOI: 10.1016/j.jaci.2020.11.046] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 10/28/2020] [Accepted: 11/24/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND Peanut allergy (PA) is the leading pediatric food allergy and a common cause of anaphylaxis. Little is known, however, on the prevalence and characteristics of PA in the adult population and whether phenotypic differences exist between adult-onset and childhood-onset PA. OBJECTIVES This study describes the current US population-level burden of adult PA. METHODS A cross-sectional food allergy survey was administered via phone and web in 2015 and 2016, resulting in nationally representative complex-survey weighted data for 40,443 adults. Reported food allergies were considered "convincing" if symptoms to specific allergens were consistent with an IgE-mediated reaction. RESULTS The prevalence of current self-reported PA was 2.9% among US adults, with 1.8% having convincing PA. Over 17% of adults with peanut allergy reported onset of their PA in adulthood. In adults with childhood-onset PA, 75.4% reported physician-diagnosed PA, compared with only 58.9% of adult-onset PA. Despite a similar frequency of food allergy-related emergency department visits within the past year (approximately 1 in 5 adults with PA allergy), adults with childhood-onset PA were significantly more likely to have a current epinephrine prescription compared with those with adult-onset PA (56% vs 44% respectively; P = .02) and were more likely to use an epinephrine autoinjector (48% vs 35%, P = .01). CONCLUSIONS Approximately 4.6 million US adults have PA-over 800,000 of whom appear to have developed their PA after age 18 years. Further examination of phenotypic differences between childhood-onset and adult-onset PA may improve understanding and management of adult PA.
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Affiliation(s)
- Christopher Warren
- Center for Food Allergy and Asthma Research, Northwestern University Feinberg School of Medicine, Chicago, Ill; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif
| | - Dawn Lei
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill
| | - Scott Sicherer
- Elliot and Roslyn Jaffe Food Allergy Institute, Division of Allergy, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY
| | - Robert Schleimer
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Ruchi Gupta
- Center for Food Allergy and Asthma Research, Northwestern University Feinberg School of Medicine, Chicago, Ill; Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill.
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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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40
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Midun E, Radulovic S, Brough H, Caubet JC. Recent advances in the management of nut allergy. World Allergy Organ J 2021; 14:100491. [PMID: 33510829 PMCID: PMC7811165 DOI: 10.1016/j.waojou.2020.100491] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 11/02/2020] [Accepted: 11/03/2020] [Indexed: 11/25/2022] Open
Abstract
Peanut/tree nut allergy is common and has been associated with particularly severe reactions. Epidemiological data have shown that the prevalence ranges between 0.05% and 4.9% for tree nut and between 0.5% and 3% for peanut. These large variations can be explained by differences in the age of included patients and the geographical region. In addition, the food consumption modality (ie, raw versus roasted) plays a major role, as heat treatment has the capacity to modify the allergenicity of nuts and legumes. Nut allergies tend to persist into adulthood and consequently have a high impact on quality of life. Recently, it has been demonstrated that a significant proportion of nut allergic patients are able to tolerate other nuts. As opposed to the avoidance of all nuts, this approach is currently proposed in several tertiary allergy centers. However, diagnosis of nut allergy is particularly difficult due to co-sensitization leading to high rate of false positive skin prick tests and/or specific IgE to whole allergen extracts. The use of component resolved diagnosis leads to major improvement of diagnosis, particularly to distinguish between primary and secondary nut allergies. The basophil activation test has been suggested to be useful but is still used mainly as a research tool. Thus, diagnosis remains mainly based on the oral food challenge, which is considered as the gold standard. Regarding treatment, avoidance remains the cornerstone of management of nut allergy. Oral immunotherapy is increasingly proposed as an alternative management strategy.
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Key Words
- Component-resolved diagnostic, CRD
- Cross reactivity
- Double-blind, placebo-controlled, food challenge, DBPCFC
- Food allergy
- Lipid transfer protein, LTP
- Oral allergy syndrome, OAS
- Oral food challenge, OFC
- Oral immunotherapy
- Oral induction tolerance, OIT
- Pathogenesis related protein type 10, PR-10
- Peanut
- Platelet-activating factor, PAF
- Pollen-food syndrome, PFS
- Precautionary Allergen Labels, (PAL)
- Skin prick test, SPT
- Tree nut
- Tree nut, TN
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Affiliation(s)
- Elise Midun
- Pediatric Allergy Unit, University Hospitals of Geneva and University of Geneva, Rue Willy Donzé 6, 1205 Geneva, Switzerland, University Lyon 1 Claude Bernard, 43 Boulevard Du 11-Novembre-1918, 69100, Villeurbanne, France
- Corresponding author.
| | - Suzana Radulovic
- Paediatric Allergy Group, Department of Women and Children's Health, King's College London, London, United Kingdom, Paediatric Allergy Group, Peter Gorer Dept of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guys' Hospital, London, United Kingdom, Children's Allergy Service, Evelina Children's Hospital, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom
| | - Helen Brough
- Paediatric Allergy Group, Department of Women and Children's Health, King's College London, London, United Kingdom, Paediatric Allergy Group, Peter Gorer Dept of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guys' Hospital, London, United Kingdom, Children's Allergy Service, Evelina Children's Hospital, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom
| | - Jean-Christoph Caubet
- Pediatric Allergy Unit, University Hospitals of Geneva and University of Geneva, Rue Willy Donzé 6, 1205, Geneva, Switzerland
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Blaiss MS, Meadows JA, Yu S, Robison DR, Hass SL, Norrett KE, Guerin A, Latremouille-Viau D, Tilles SA. Economic burden of peanut allergy in pediatric patients with evidence of reactions to peanuts in the United States. J Manag Care Spec Pharm 2021; 27:516-527. [PMID: 33470880 PMCID: PMC10394212 DOI: 10.18553/jmcp.2021.20389] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND: The economic burden of food allergy is large; however, costs specific to individuals with peanut allergy experiencing reactions to peanuts remain to be evaluated. As the prevalence of peanut allergy continues to increase in children, a better understanding of the cost of care is warranted. OBJECTIVE: To assess the cost of care of peanut allergy among privately insured and Medicaid-insured pediatric patients in the United States. METHODS: This retrospective matched-cohort study included patients aged 4-17 years from the Optum Health Care Solutions and Medicaid Claims databases (January 1, 2007-March 31, 2017). Patients were classified into 2 cohorts: peanut allergy (with peanut allergy diagnosis codes and reactions triggering health care resource utilization [HRU]) and peanut allergy-free (no peanut allergy diagnosis codes in claims). Peanut allergy patients were matched 1:10 to peanut allergy-free patients based on baseline covariates. Comorbidities including anxiety and depression, HRU, and direct health care costs were compared between cohorts and reported for both perspectives separately. RESULTS: Compared with peanut allergy-free patients (n = 30,840 privately insured; n = 12,450 Medicaid), peanut allergy patients (n = 3,084 privately insured; n = 1,245 Medicaid) had higher prevalence of asthma, atopic dermatitis/eczema, other food allergies, allergic rhinitis, depression, and anxiety (all P < 0.01). Peanut allergy patients had higher HRU per patient per year (PPPY), including 90% more emergency department visits among both privately insured and Medicaid patients (P < 0.01) and higher direct health care costs PPPY, with incremental costs of $2,247 total or $1,712 excluding asthma-related costs for privately insured patients and $2,845 total or $1,844 excluding asthma-related costs for Medicaid patients (all P < 0.01). CONCLUSIONS: Pediatric patients in the United States with peanut allergy and reactions triggering HRU had significantly higher comorbidity burdens, HRU, and direct health care costs, regardless of asthma-related costs, versus those without peanut allergy. DISCLOSURES: This study was funded by Aimmune Therapeutics, a Nestlé Health Science company. The study sponsor was involved in several aspects of the research including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication. Yu and Tilles are employees of Aimmune Therapeutics, a Nestlé Health Science company. Robison and Norrett were employees of Aimmune Therapeutics at the time this study was conducted. Blaiss, Meadows, and Hass provided paid consulting services to Aimmune Therapeutics. Guerin and Latremouille-Viau are employees of Analysis Group, a consulting company that provided paid consulting services to Aimmune Therapeutics. Parts of the results were presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting held March 25-28, 2019, in San Diego, CA, and at the ISPOR Annual Meeting held May 18-22, 2019, in New Orleans, LA.
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Affiliation(s)
| | | | - Shengsheng Yu
- Aimmune Therapeutics, a Nestlé Health Science company, Brisbane, CA
| | - Dan R Robison
- Aimmune Therapeutics, a Nestlé Health Science company, Brisbane, CA
| | | | - Kevin E Norrett
- Aimmune Therapeutics, a Nestlé Health Science company, Brisbane, CA
| | | | | | - Stephen A Tilles
- Aimmune Therapeutics, a Nestlé Health Science company, Brisbane, CA
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42
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Cox AL, Eigenmann PA, Sicherer SH. Clinical Relevance of Cross-Reactivity in Food Allergy. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2021; 9:82-99. [PMID: 33429724 DOI: 10.1016/j.jaip.2020.09.030] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 09/23/2020] [Accepted: 09/23/2020] [Indexed: 02/07/2023]
Abstract
The diagnosis and management of food allergy is complicated by an abundance of homologous, cross-reactive proteins in edible foods and aeroallergens. This results in patients having allergic sensitization (positive tests) to many biologically related foods. However, many are sensitized to foods without exhibiting clinical reactivity. Although molecular diagnostics have improved our ability to identify clinically relevant cross-reactivity, the optimal approach to patients requires an understanding of the epidemiology of clinically relevant cross-reactivity, as well as the food-specific (degree of homology, protein stability, abundance) and patient-specific factors (immune response, augmentation factors) that determine clinical relevance. Examples of food families with high rates of cross-reactivity include mammalian milks, eggs, fish, and shellfish. Low rates are noted for grains (wheat, barley, rye), and rates of cross-reactivity are variable for most other foods. This review discusses clinically relevant cross-reactivity related to the aforementioned food groups as well as seeds, legumes (including peanut, soy, chickpea, lentil, and others), tree nuts, meats, fruits and vegetables (including the lipid transfer protein syndrome), and latex. The complicating factor of addressing co-allergy, for example, the risks of allergy to both peanut and tree nuts among atopic patients, is also discussed. Considerations for an approach to individual patient care are highlighted.
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Affiliation(s)
- Amanda L Cox
- Division of Allergy and Immunology, Department of Pediatrics, Elliot and Roslyn Jaffe Food Allergy Institute, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, NY.
| | - Philippe A Eigenmann
- The Department of Pediatrics Gynecology and Obstetrics, Medical School of the University of Geneva, University Hospitals of Geneva, Geneva, Switzerland
| | - Scott H Sicherer
- Division of Allergy and Immunology, Department of Pediatrics, Elliot and Roslyn Jaffe Food Allergy Institute, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, NY
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43
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Abstract
Peanut (PN) allergy is a common life-threatening disease; however, our knowledge on the immunological mechanisms remains limited. Here, we describe the first mouse model of inhalation-driven peanut allergy. We administered PN flour intranasally to naïve wild-type mice twice a week for 4 weeks, followed by intraperitoneal challenge with PN extract. Exposure of mice to PN flour sensitized them without addition of adjuvants, and mice developed PN-specific IgE, IgG1, and IgG2a. After challenge, mice displayed lower body temperature and other clinical signs of anaphylaxis. This inhalation model is an ideal system to allow for future examination of immunological mechanisms critical for the development of PN allergy.
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Affiliation(s)
- Joseph J Dolence
- Department of Biology, University of Nebraska at Kearney, Kearney, NE, USA.
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44
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Schoos AMM, Bullens D, Chawes BL, Costa J, De Vlieger L, DunnGalvin A, Epstein MM, Garssen J, Hilger C, Knipping K, Kuehn A, Mijakoski D, Munblit D, Nekliudov NA, Ozdemir C, Patient K, Peroni D, Stoleski S, Stylianou E, Tukalj M, Verhoeckx K, Zidarn M, van de Veen W. Immunological Outcomes of Allergen-Specific Immunotherapy in Food Allergy. Front Immunol 2020; 11:568598. [PMID: 33224138 PMCID: PMC7670865 DOI: 10.3389/fimmu.2020.568598] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 09/30/2020] [Indexed: 12/21/2022] Open
Abstract
IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures.
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Affiliation(s)
- Ann-Marie Malby Schoos
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
- Department of Pediatrics, Slagelse Sygehus, Slagelse, Denmark
| | - Dominique Bullens
- Allergy and Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Clinical Division of Pediatrics, UZ Leuven, Leuven, Belgium
| | - Bo Lund Chawes
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Joana Costa
- REQUIMTE-LAQV, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
| | - Liselot De Vlieger
- Allergy and Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Audrey DunnGalvin
- School of Applied Psychology, University College Cork, Cork, Ireland
- Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Michelle M. Epstein
- Experimental Allergy Laboratory, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
- Centre of Excellence Immunology, Danone Nutricia research, Utrecht, Netherlands
| | - Christiane Hilger
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Karen Knipping
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
- Centre of Excellence Immunology, Danone Nutricia research, Utrecht, Netherlands
| | - Annette Kuehn
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Dragan Mijakoski
- Institute of Occupational Health of RNM, Skopje, North Macedonia
- Faculty of Medicine, Ss. Cyril and Methodius, University in Skopje, Skopje, North Macedonia
| | - Daniel Munblit
- Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Inflammation, Repair and Development Section, NHLI, Imperial College London, London, United Kingdom
| | - Nikita A. Nekliudov
- Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Cevdet Ozdemir
- Institute of Child Health, Department of Pediatric Basic Sciences, Istanbul University, Istanbul, Turkey
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Karine Patient
- SPI—Food Allergy Unit, Département Médicaments et Technologies pour la Santé (DMTS), Université Paris Saclay, CEA, INRAE, Gif-sur-Yvette, France
| | - Diego Peroni
- Section of Pediatrics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Sasho Stoleski
- Institute of Occupational Health of RNM, Skopje, North Macedonia
- Faculty of Medicine, Ss. Cyril and Methodius, University in Skopje, Skopje, North Macedonia
| | - Eva Stylianou
- Regional Unit for Asthma, Allergy and Hypersensitivity, Department of Pulmonary Diseases, Oslo University Hospital, Oslo, Norway
| | - Mirjana Tukalj
- Children’s Hospital, Department of Allergology and Pulmonology, Zagreb, Croatia
- Faculty of Medicine, University of Osijek, Osijek, Croatia
- Catholic University of Croatia, Zagreb, Croatia
| | - Kitty Verhoeckx
- Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Mihaela Zidarn
- University Clinic of Pulmonary and Allergic Diseases Golnik, Golnik, Slovenia, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Willem van de Veen
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
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Dolence JJ, Kita H. Allergic sensitization to peanuts is enhanced in mice fed a high-fat diet. AIMS ALLERGY AND IMMUNOLOGY 2020; 4:88-99. [PMID: 38304556 PMCID: PMC10831907 DOI: 10.3934/allergy.2020008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2024] Open
Abstract
The incidence of peanut (PN) allergy is on the rise. As peanut allergy rates have continued to climb over the past few decades, obesity rates have increased to record highs, suggesting a link between obesity and the development of peanut allergy. While progress has been made, much remains to be learned about the mechanisms driving the development of allergic immune responses to peanut. Remaining unclear is whether consuming a Western diet, a diet characterized by overeating foods rich in saturated fat, salt, and refined sugars, supports the development of PN allergy. To address this, we fed mice a high fat diet to induce obesity. Once diet-induced obesity was established, mice were exposed to PN flour via the airways using our 4-week inhalation model. Mice were subsequently challenged with PN extract to induce anaphylaxis. Mice fed a high-fat diet developed significantly higher titers of PN-specific IgE, as well as stronger anaphylactic responses, when compared to their low-fat diet fed counterparts. These results suggest that obesity linked to eating a high-fat diet promotes the development of allergic immune responses to PN in mice. Such knowledge is critical to advance our growing understanding of the immunology of PN allergy.
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Affiliation(s)
- Joseph J. Dolence
- Department of Biology, University of Nebraska at Kearney, Kearney, NE 68849
| | - Hirohito Kita
- Department of Medicine and Immunology, Mayo Clinic Scottsdale, Scottsdale, AZ 85259
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Zhang Y, Jin T. Almond allergens: update and perspective on identification and characterization. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2020; 100:4657-4663. [PMID: 32270879 DOI: 10.1002/jsfa.10417] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 04/01/2020] [Accepted: 04/09/2020] [Indexed: 06/11/2023]
Abstract
Almond (Prunus dulcis) is not only widely used as a human food as a result of its flavor, nutrients, and health benefits, but it is also one of the most likely tree nuts to trigger allergies. Almond allergens, however, have not been studied as extensively as those of peanuts and other selected tree nuts. This review provides an update of the molecular properties of almond allergens to clarify some confusion about the identities of almond allergens and our perspective on characterizing putative almond allergens. At present, the following almond allergens have been designated by the World Health Organization/International Union of Immunological Societies Allergen Nomenclature Sub-Committee: Pru du 3 (a non-specific lipid transfer protein 1, nsLTP1), Pru du 4 (a profilin), Pru du 5 (60S acidic ribosomal protein 2), Pru du 6 (an 11S legumin known as prunin) and Pru du 8 (an antimicrobial protein with cC3C repeats). Besides, almond vicilin and almond γ-conglutin have been identified as food allergens, although further characterization of these allergens is still of interest. In addition, almond 2S albumin was reported as a food allergen as a result of the misidentification of Pru du 8. Two more almond proteins have been called allergens based on their sequence homology with known food allergens and their 'membership' in relevant protein families that contain allergens in many species. These include the pathogenesis related-10 protein (referred to as Pru du 1) and the thaumatin-like protein (referred to as Pru du 2). Almonds thus have five known food allergens and five more likely ones that need to be investigated further. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
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Affiliation(s)
- Yuzhu Zhang
- U.S. Department of Agriculture, Agricultural Research Service, Pacific West Area, Western Regional Research Center, Albany, CA, USA
| | - Tengchuan Jin
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
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Chebar Lozinsky A, Loke P, Orsini F, O'Sullivan M, L Prescott S, Gold MS, Quinn P, DunnGalvin A, Lk Tang M. Study protocol of a multicentre, randomised, controlled trial evaluating the effectiveness of probiotic and peanut oral immunotherapy (PPOIT) in inducing desensitisation or tolerance in children with peanut allergy compared with oral immunotherapy (OIT) alone and with placebo (the PPOIT-003 study). BMJ Open 2020; 10:e035871. [PMID: 32912942 PMCID: PMC7482477 DOI: 10.1136/bmjopen-2019-035871] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION Peanut allergy is the the most common cause of life-threatening food-induced anaphylaxis. There is currently no effective long-term treatment. There is a pressing need for definitive treatments that improve the quality of life and prevent fatalities. Allergen oral immunotherapy (OIT) is a promising approach, which is effective at inducing desensitisation; however, OIT has a limited ability to induce sustained unresponsiveness (SU). We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut OIT (Probiotic Peanut Oral ImmunoTherapy (PPOIT)) is highly effective at inducing SU, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. Here we describe the protocol for a Phase IIb multicentre, double-blind, randomised, controlled trial (PPOIT-003) with dual primary objectives to evaluate the effectiveness of PPOIT at inducing SU (assessed at 8 weeks after treatment cessation) compared with placebo treatment and peanut OIT alone, in children with peanut allergy. METHODS AND ANALYSIS 200 children 1 to 10 years of age with current peanut allergy confirmed by failed double-blind placebo-controlled food challenge (DBPCFC) at study screening will be recruited from three tertiary paediatric hospitals in Australia. There are three intervention arms-PPOIT, peanut OIT alone or placebo. Interventions are administered once daily for 18 months. The dual primary outcomes are: (1) the proportion of children who attain 8-week SU in the PPOIT group versus placebo group and (2) the proportion of children who attain 8-week SU in the PPOIT group versus OIT group. ETHICS AND DISSEMINATION This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 35246) and the Child and Adolescent Health Service (RGS 2543). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. TRIAL REGISTRATION NUMBER ACTRN12616000322437.
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Affiliation(s)
| | - Paxton Loke
- Allergy Immunology, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Allergy and Immunology, Royal Children's Hospital, Melbourne, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Francesca Orsini
- Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Clinical Epidemiology and Biostatistics Unit, Melbourne Children's Trial Centre, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
| | - Michael O'Sullivan
- ORIGINS Project, Telethon Kids Institute, Nedlands, Western Australia, Australia
- Division of Pathology and Laboratory Medicine, School of Medicine, University of Western Australia, Crawley, Western Australia, Australia
- Allergy, Immunology and Dermatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
| | - Susan L Prescott
- ORIGINS Project, Telethon Kids Institute, Nedlands, Western Australia, Australia
- Allergy, Immunology and Dermatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
- Division of Paediatrics, School of Medicine, University of Western Australia, Perth, Western Australia, Australia
| | - Michael S Gold
- Paediatrics, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
- Allergy and Immunology, Women's and Children's Hospital, North Adelaide, South Australia, Australia
| | - Patrick Quinn
- Paediatrics, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
- Allergy and Immunology, Women's and Children's Hospital, North Adelaide, South Australia, Australia
| | - Audrey DunnGalvin
- School of Applied Psychology, University College Cork, Cork, Ireland
- Institute of Child Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Mimi Lk Tang
- Allergy Immunology, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Allergy and Immunology, Royal Children's Hospital, Melbourne, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
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48
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Venter C, Sicherer SH, Greenhawt M. Management of Peanut Allergy. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2020; 7:345-355.e2. [PMID: 30717865 DOI: 10.1016/j.jaip.2018.10.043] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 10/22/2018] [Accepted: 10/23/2018] [Indexed: 01/14/2023]
Abstract
Peanut allergy is a growing public health concern in westernized countries. Peanut allergy is characterized as an often severe and lifelong allergy, which can have detrimental effects on quality of life and trigger anxiety. Although multiple therapeutic options are emerging, the focus of current management strategies is strict peanut avoidance and carriage of self-injectable epinephrine. The greatest risk of reacting to peanut comes from direct ingestion, whereas casual skin contact or airborne exposure is highly unlikely to provoke significant symptoms. Patients and families must be educated about how to best execute strict peanut avoidance through careful label reading as well as how to understand and address likely and unlikely risk with regard to peanut exposure in public, in particular when dining outside of the home and for children attending school or child care. This review discusses the risk of exposure in public such as at school or on an airplane and how such risk can be abated, situations and scenarios when dining out of the house that may pose more risks than others, the essentials of US and EU label reading laws with particular emphasis on precautionary labeling and the risk implied by such, quality of life and psychosocial issues that may affect the peanut allergic individual and family, and a discussion of how risk may differ and evolve based on the patient's age.
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Affiliation(s)
- Carina Venter
- Section of Allergy and Immunology, Children's Hospital Colorado, Food Challenge and Research Unit, University of Colorado School of Medicine, Aurora, Colo; The David Hide Asthma and Allergy Research Centre, Newport, Isle of Wight, United Kingdom.
| | - Scott H Sicherer
- Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai and the Jafee Food Allergy Institute, New York, NY
| | - Matthew Greenhawt
- Section of Allergy and Immunology, Children's Hospital Colorado, Food Challenge and Research Unit, University of Colorado School of Medicine, Aurora, Colo
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49
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Abstract
Urticaria and, to a lesser extent, angioedema are common occurrences in the pediatric population. There are multiple causes of acute and chronic urticaria and angioedema. Most causes are benign, although they can be worrisome for patients and their parents. An allergist should evaluate acute urticaria and/or angioedema if there are concerns of an external cause, such as foods or medications. Chronic urticaria and angioedema can severely affect quality of life and should be managed aggressively with antihistamines and immunomodulators if poorly controlled. Chronic symptoms are unlikely to be due to an external cause. Anaphylaxis is a more serious allergic condition characterized by a systemic reaction involving at least 2 organ systems. Anaphylaxis should be initially managed with intramuscular epinephrine. Patients who experience anaphylaxis should be evaluated by an allergist for possible causes; if found, avoidance of the inciting antigen is the best management. All patients should also be given an epinephrine autoinjector and an action plan. Foods are a common cause of anaphylaxis in the pediatric population. New evidence suggests that the introduction of highly allergic foods is safe in infancy and should not be delayed. In addition, the early introduction of foods such as peanuts may help prevent the development of food allergies.
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Affiliation(s)
| | - Theresa A Bingemann
- University of Rochester, Rochester, NY.,Department of Allergy, Immunology, and Rheumatology, Rochester Regional Health, Rochester, NY
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50
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Clarke AE, Elliott SJ, St Pierre Y, Soller L, La Vieille S, Ben-Shoshan M. Comparing food allergy prevalence in vulnerable and nonvulnerable Canadians. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2020; 8:2425-2430.e11. [PMID: 32304831 DOI: 10.1016/j.jaip.2020.03.037] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 02/21/2020] [Accepted: 03/18/2020] [Indexed: 01/02/2023]
Affiliation(s)
- Ann E Clarke
- Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
| | - Susan J Elliott
- Department of Geography and Environmental Management, University of Waterloo, Waterloo, ON, Canada
| | - Yvan St Pierre
- Division of Clinical Epidemiology, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada
| | - Lianne Soller
- Division of Allergy and Immunology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Sebastien La Vieille
- Bureau of Chemical Safety, Health Canada, Ottawa, ON, Canada; Food Science Department, Faculty of Agricultural and Nutrition Sciences, Laval University, Quebec City, QC, Canada
| | - Moshe Ben-Shoshan
- Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada
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