Sustained successful peanut oral immunotherapy associated with low basophil activation and peanut-specific IgE

Tsai, Mindy; Mukai, Kaori; Chinthrajah, R. Sharon; Nadeau, Kari; Galli, Stephen J.

doi:10.1016/j.jaci.2019.10.038

Cited by 94 publications

(104 citation statements)

References 49 publications

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“…For instance, patients undergoing OIT for peanut allergy in the PRROTECT trial had several log increases in levels of peanut-specific IgG1, IgG2, IgG3, IgG4, and IgA, as well as the ratio of peanut-specific IgG4/IgE with the greatest increases evident in peanut-specific IgG2 and IgG4 which were increased by two logs (139,174). The groups of Galli and Nadeau reported that robust IgG responses and elevated IgG4/IgE ratios correlate with sustained unresponsiveness following peanut OIT (175). When modeled in mice with established peanut allergy, OIT also induces a strong IgG response, inclusive of all the murine IgG subclasses (174).…”

Section: Induction Of High Levels Of Specific Igg Following Oitmentioning

confidence: 99%

IgE and IgG Antibodies as Regulators of Mast Cell and Basophil Functions in Food Allergy

et al. 2020

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Food allergy is a major health issue, affecting the lives of 8% of U.S. children and their families. There is an urgent need to identify the environmental and endogenous signals that induce and sustain allergic responses to ingested allergens. Acute reactions to foods are triggered by the activation of mast cells and basophils, both of which release inflammatory mediators that lead to a range of clinical manifestations, including gastrointestinal, cutaneous, and respiratory reactions as well as systemic anaphylaxis. Both of these innate effector cell types express the high affinity IgE receptor, FcϵRI, on their surface and are armed for adaptive antigen recognition by very-tightly bound IgE antibodies which, when cross-linked by polyvalent allergen, trigger degranulation. These cells also express inhibitory receptors, including the IgG Fc receptor, FcγRIIb, that suppress their IgE-mediated activation. Recent studies have shown that natural resolution of food allergies is associated with increasing food-specific IgG levels. Furthermore, oral immunotherapy, the sequential administration of incrementally increasing doses of food allergen, is accompanied by the strong induction of allergen-specific IgG antibodies in both human subjects and murine models. These can deliver inhibitory signals via FcγRIIb that block IgE-induced immediate food reactions. In addition to their role in mediating immediate hypersensitivity reactions, mast cells and basophils serve separate but critical functions as adjuvants for type 2 immunity in food allergy. Mast cells and basophils, activated by IgE, are key sources of IL-4 that tilts the immune balance away from tolerance and towards type 2 immunity by promoting the induction of Th2 cells along with the innate effectors of type 2 immunity, ILC2s, while suppressing the development of regulatory T cells and driving their subversion to a pathogenic pro-Th2 phenotype. This adjuvant effect of mast cells and basophils is suppressed when inhibitory signals are delivered by IgG antibodies signaling via FcγRIIb. This review summarizes current understanding of the immunoregulatory effects of mast cells and basophils and how these functions are modulated by IgE and IgG antibodies. Understanding these pathways could provide important insights into innovative strategies for preventing and/or reversing food allergy in patients.

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Section: Induction Of High Levels Of Specific Igg Following Oitmentioning

confidence: 99%

IgE and IgG Antibodies as Regulators of Mast Cell and Basophil Functions in Food Allergy

et al. 2020

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“…Increased tolerability of basophils to Parietaria allergen (CD-Sens measured by CD63 and CD203c) and a significantly reduced symptom severity were observed in AR patients treated with SLIT [171]. Further, significantly decreased basophil activation was also observed after peanut OIT (Peanut oral immunotherapy study: safety, efficacy and discovery -POISED study) and this is correlated to higher sIgG4/ sIgE ratio and the study suggested that patients with low basophil responsiveness were more likely to achieve treatment success to peanut OIT [172]. Similarly, there was significant decrease in basophil sensitivity to Ara h 2 peanut allergen in patients with sustained unresponsiveness after peanut OIT [173].…”

Section: Effects On Mcs Eosinophils Basophils Ilc2s and Dcsmentioning

confidence: 91%

Mechanisms of allergen-specific immunotherapy for allergic rhinitis and food allergies

2020

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Allergen-specific immunotherapy (AIT) is currently the only potential treatment for allergies including allergic rhinitis (AR) and food allergies (FA) that can modify the underlying course of the diseases. Although AIT has been performed for over a century, the precise and detailed mechanism for AIT is still unclear. Previous clinical trials have reported that successful AIT induces the reinstatement of tolerance against the specific allergen. In this review, we aim to provide an updated summary of the knowledge on the underlying mechanisms of IgE-mediated AR and FA as well as the immunological changes observed after AIT and discuss on how better understanding of these can lead to possible identification of biomarkers and novel strategies for AIT.

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“…Reliable identification of each phenotype before starting therapy remains a substantial research goal, and great strides are being made on this front. 17 In addition, there may be variability among patients/caregivers about their goals for therapy, for example, protection against cross-contamination (''may contain'' foods); protection from larger accidental exposures (''bite-proof protection''); or regular ingestion of the food (''free eating''). As much as possible, each family's treatment goal and the individualized maintenance dose of OIT required to achieve that goal should be clarified in advance for non-FDA-approved products.…”

Section: Goals Of Therapymentioning

confidence: 99%

Consensus report from the Food Allergy Research & Education (FARE) 2019 Oral Immunotherapy for Food Allergy Summit

Pepper

Assa’ad

Blaiss

et al. 2020

Journal of Allergy and Clinical Immunology

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Sustained successful peanut oral immunotherapy associated with low basophil activation and peanut-specific IgE

Cited by 94 publications

References 49 publications

IgE and IgG Antibodies as Regulators of Mast Cell and Basophil Functions in Food Allergy

IgE and IgG Antibodies as Regulators of Mast Cell and Basophil Functions in Food Allergy

Mechanisms of allergen-specific immunotherapy for allergic rhinitis and food allergies

Consensus report from the Food Allergy Research & Education (FARE) 2019 Oral Immunotherapy for Food Allergy Summit

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