Stepwise oral immunotherapy for 10 days in an egg-white allergy mouse model did not ameliorate the severity of allergy but induced the production of allergen-specific IgA

Maeta, Akihiro; Katahira, Risako; Marin, Mariana; Onishi, Haruka; Nakamura, Yu; Takahashi, Kyoko

doi:10.1080/09168451.2018.1517592

Cited by 4 publications

(5 citation statements)

References 12 publications

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“…We initially found marked increases in allergen-specific IgA in a trial of OIT for peanut an observation that has subsequently been extended by others to cow’s milk and egg OIT ( 14 , 32 – 35 ). Murine models have also documented specific IgA responses following food allergen ingestion and OIT ( 24 , 36 – 38 ). Despite the consistent observation of association between IgA responses and food tolerance in humans and in murine models of food allergy, neither the direct contributions of IgA to tolerance nor the mechanisms thereof have been established.…”

Section: Discussionmentioning

confidence: 99%

Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils

Kanagaratham¹,

Burton²,

Santos³

et al. 2022

Front. Immunol.

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Mast cells and basophils have long been implicated in the pathogenesis of IgE-mediated hypersensitivity reactions. They express the high-affinity IgE receptor, FcϵRI, on their surface. Antigen-induced crosslinking of IgE antibodies bound to that receptor triggers a signaling cascade that results in activation, leading to the release of an array of preformed vasoactive mediators and rapidly synthesized lipids, as well as the de novo production of inflammatory cytokines. In addition to bearing activating receptors like FcεRI, these effector cells of allergy express inhibitory ones including FcγR2b, an IgG Fc receptor with a cytosolic inhibitory motif that activates protein tyrosine phosphatases that suppress IgE-mediated activation. We and others have shown that food allergen-specific IgG antibodies strongly induced during the course of oral immunotherapy (OIT), signal via FcγR2b to suppress IgE-mediated mast cell and basophil activation triggered by food allergen challenge. However, the potential inhibitory effects of IgA antibodies, which are also produced in response to OIT and are present at high levels at mucosal sites, including the intestine where food allergens are encountered, have not been well studied. Here we uncover an inhibitory function for IgA. We observe that IgA binds mouse bone marrow-derived mast cells (BMMCs) and peritoneal mast cells. Binding to BMMCs is dependent on calcium and sialic acid. We also found that IgA antibodies inhibit IgE-mediated mast cell degranulation in an allergen-specific fashion. Antigen-specific IgA inhibits IgE-mediated mast cell activation early in the signaling cascade, suppressing the phosphorylation of Syk, the proximal protein kinase mediating FcεRI signaling, and suppresses mast cell production of cytokines. Furthermore, using basophils from a peanut allergic donor we found that IgA binds to basophils and that activation by exposure to peanuts is effectively suppressed by IgA. We conclude that IgA serves as a regulator of mast cell and basophil degranulation, suggesting a physiologic role for IgA in the maintenance of immune homeostasis at mucosal sites.

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Section: Discussionmentioning

confidence: 99%

Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils

Kanagaratham¹,

Burton²,

Santos³

et al. 2022

Front. Immunol.

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“…[22][23][24] Over the past few years, different groups demonstrated that induction of other antibody isotypes, such as IgA, IgG 1 , IgG 4 , and IgD, can ameliorate IgE-mediated reactions. 15,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Specifically, several clinical trials of egg oral immunotherapy reported increases of serum antigen-specific IgA, IgG 1 , and IgG 4 in patients that responded to treatment. 32,33 Interestingly, the ability of the antibodies to block IgE-mediated responses could be largely dependent on their antigen specificity rather than isotype.…”

Section: Introductionmentioning

confidence: 99%

“…Over the past few years, different groups demonstrated that induction of other antibody isotypes, such as IgA, IgG 1 , IgG 4 , and IgD, can ameliorate IgE‐mediated reactions 15,25‐40 . Specifically, several clinical trials of egg oral immunotherapy reported increases of serum antigen‐specific IgA, IgG 1 , and IgG 4 in patients that responded to treatment 32,33 .…”

Section: Introductionmentioning

confidence: 99%

Ovomucoid epitope‐specific repertoire of IgE, IgG₄, IgG₁, IgA₁, and IgD antibodies in egg‐allergic children

Suprun

Getts

Grishina

et al. 2020

Allergy

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Background: Egg-white ovomucoid, that is, Gal d 1, is associated with IgE-mediated allergic reactions in most egg-allergic children. Epitope-specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibody isotypes (IgG 1 , IgG 4 , IgA , and IgD) may have a protective function; yet, their epitope-specific repertoires and associations with atopic comorbidities have not been studied. Methods: Bead-based epitope assay (BBEA) was used to quantitate the levels of epitope-specific (es)IgA, esIgE, esIgD, esIgG 1 , and esIgG 4 antibodies directed at 58 (15-mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg-allergic and 6 atopic children. Intraclass correlation (ICC) and coefficient of variation (CV) were used for the reliability assessment. The relationships across esIgs were evaluated using network analysis; linear and logistic regressions were used to compare groups based on egg allergy status and comorbidities. Results: BBEA had high reliability (ICC >0.75) and low variability (CV <20%) and could detect known IgE-binding epitopes. Egg-allergic children had lower esIgA 1 (P = .010) and esIgG 1 (P = .016) and higher esIgE (P < .001) and esIgD (P = .015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher esIgD had decreased odds of anaphylactic reactions (OR =0.48, P = .038). Network analysis identified most associations between esIgE with either esIgG 4 or esIgD; indicating that IgE-secreting plasma cells could originate from either sequential isotype switch from antigen-experienced intermediate isotypes or directly from the IgD + B cells. Conclusions: Collectively, these data point toward a contribution of epitope-specific antibody repertoires to the pathogenesis of egg allergy.

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“…In an allergic mouse model, animals sensitized with egg white have given information about IgA in AIT. After 12 days of administration, allergen-specific IgA levels were higher in OIT mouse with short-term treatment [77]. A recent human OIT study has reported that during egg OIT, egg-and component-specific IgA, IgA1 and IgA2 levels in plasma also increased in patients who responded to therapy.…”

Section: Relationship Among the Responses Of Ige Igg And Igamentioning

confidence: 92%

Diverse Mechanisms of Allergen Specific Immunotherapy

Cevhertas

Лацин

Akdiş

et al. 2019

Vestn. Ross. univ. družby nar., Ser. Med.

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Allergen immunotherapy (AIT) is widely used to establish a tolerant immune response and it is currently the only disease modifying treatment. There are different routes to administer the allergen, including subcutaneous, sublingual, intralymphatic, epicutaneous, intradermal, and oral and local nasal allergen immunotherapy. Although the optimal administration route depends on the type of allergen, some patients remain unresponsive and so it is important to predict the outcome before and during treatment. Therefore, there is a need to identify candidate prognostic markers for allergen immunotherapy. Herein, we discuss the recent literature on the molecular mechanisms of AIT.

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Stepwise oral immunotherapy for 10 days in an egg-white allergy mouse model did not ameliorate the severity of allergy but induced the production of allergen-specific IgA

Cited by 4 publications

References 12 publications

Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils

Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils

Ovomucoid epitope‐specific repertoire of IgE, IgG₄, IgG₁, IgA₁, and IgD antibodies in egg‐allergic children

Diverse Mechanisms of Allergen Specific Immunotherapy

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Stepwise oral immunotherapy for 10 days in an egg-white allergy mouse model did not ameliorate the severity of allergy but induced the production of allergen-specific IgA

Cited by 4 publications

References 12 publications

Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils

Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils

Ovomucoid epitope‐specific repertoire of IgE, IgG4, IgG1, IgA1, and IgD antibodies in egg‐allergic children

Diverse Mechanisms of Allergen Specific Immunotherapy

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Product

Resources

About

Ovomucoid epitope‐specific repertoire of IgE, IgG₄, IgG₁, IgA₁, and IgD antibodies in egg‐allergic children