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Changes in passively-sensitized basophil activation to ?S1-casein after oral immunotherapy.

ABSTRACT: INTRODUCTION:Immune response to cow's milk allergen (CMA) has been analyzed mostly using crude milk antigen or a mixture of various caseins. This study aimed to assess the changes in the immunological response against ?S1-casein during oral immunotherapy (OIT) and to investigate the mechanism of tolerance. METHODS:We have performed rush OIT to 39 patients with CMA and obtained the serum samples up to 3 years after OIT. Immunoglobulin E (IgE) and IgG4 antibodies specific to highly purified ?S1-casein as well as passively-sensitized basophil activation were evaluated using the serial samples. Furthermore, we examined whether basophil activation led by the pre-OIT serum was suppressed by the post-OIT serum, or by the tolerant serum obtained from naturally outgrown patients. RESULTS:Specific IgE to ?S1-casein was significantly reduced after OIT. Specific IgG4 (sIgG4) to ?S1-casein was also detected in most of the pre-OIT sera, which was not significantly increased after OIT. Activation of passively-sensitized basophils to ?S1-casein was significantly reduced after 2 years (14%?±?19%) and 3 years (19%?±?18%) post-OIT compared with pre-OIT (%CD63high basophils; 51%?±?27%). Furthermore, the addition of post-OIT or tolerant serum to pre-OIT serum significantly suppressed the basophil activation. This suppression was abrogated by washing the supernatant after passive sensitization, but not by depleting IgG antibodies from post-OIT or tolerant sera, nor by blocking Fc?RIIb using an anti-Fc?R antibody. CONCLUSIONS:?S1-casein-sIgG4 plays a minor role in tolerance mechanisms in cases of CMA; humoral factors other than antigen-sIgG4 may be involved.

SUBMITTER: Matsui T

PROVIDER: S-EPMC7212200 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Changes in passively-sensitized basophil activation to αS1-casein after oral immunotherapy.

Matsui Teruaki T Naito Michihiro M Tagami Kazunori K Tajima Iwao I Teshigawara Miyuki M Makino Atsushi A Kitamura Katsumasa K Takasato Yoshihiro Y Sugiura Shiro S Yamada Chikako C Izumi Hidehiko H Tsuge Ikuya I Kondo Yasuto Y Ito Komei K

Immunity, inflammation and disease 20200303 2

<h4>Introduction</h4>Immune response to cow's milk allergen (CMA) has been analyzed mostly using crude milk antigen or a mixture of various caseins. This study aimed to assess the changes in the immunological response against αS1-casein during oral immunotherapy (OIT) and to investigate the mechanism of tolerance.<h4>Methods</h4>We have performed rush OIT to 39 patients with CMA and obtained the serum samples up to 3 years after OIT. Immunoglobulin E (IgE) and IgG4 antibodies specific to highly ...[more]

PMID: 32125071

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Project description:BackgroundMost children with detectable peanut-specific IgE (P-sIgE) are not allergic to peanut. We addressed 2 non-mutually exclusive hypotheses for the discrepancy between allergy and sensitization: (1) differences in P-sIgE levels between children with peanut allergy (PA) and peanut-sensitized but tolerant (PS) children and (2) the presence of an IgE inhibitor, such as peanut-specific IgG4 (P-sIgG4), in PS patients.MethodsTwo hundred twenty-eight children (108 patients with PA, 77 PS patients, and 43 nonsensitized nonallergic subjects) were studied. Levels of specific IgE and IgG4 to peanut and its components were determined. IgE-stripped basophils or a mast cell line were used in passive sensitization activation and inhibition assays. Plasma of PS subjects and patients submitted to peanut oral immunotherapy (POIT) were depleted of IgG4 and retested in inhibition assays.ResultsBasophils and mast cells sensitized with plasma from patients with PA but not PS patients showed dose-dependent activation in response to peanut. Levels of sIgE to peanut and its components could only partially explain differences in clinical reactivity between patients with PA and PS patients. P-sIgG4 levels (P = .023) and P-sIgG4/P-sIgE (P < .001), Ara h 1-sIgG4/Ara h 1-sIgE (P = .050), Ara h 2-sIgG4/Ara h 2-sIgE (P = .004), and Ara h 3-sIgG4/Ara h 3-sIgE (P = .016) ratios were greater in PS children compared with those in children with PA. Peanut-induced activation was inhibited in the presence of plasma from PS children with detectable P-sIgG4 levels and POIT but not from nonsensitized nonallergic children. Depletion of IgG4 from plasma of children with PS (and POIT) sensitized to Ara h 1 to Ara h 3 partially restored peanut-induced mast cell activation (P = .007).ConclusionsDifferences in sIgE levels and allergen specificity could not justify the clinical phenotype in all children with PA and PS children. Blocking IgG4 antibodies provide an additional explanation for the absence of clinical reactivity in PS patients sensitized to major peanut allergens.

Dataset Information

Changes in passively-sensitized basophil activation to ?S1-casein after oral immunotherapy.

Publications

Changes in passively-sensitized basophil activation to αS1-casein after oral immunotherapy.

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