Abstract
IntroductionImmune 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.MethodsWe 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 αS1‐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.ResultsSpecific IgE to αS1‐casein was significantly reduced after OIT. Specific IgG4 (sIgG4) to αS1‐casein was also detected in most of the pre‐OIT sera, which was not significantly increased after OIT. Activation of passively‐sensitized basophils to αS1‐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 FcγRIIb using an anti‐FcγR antibody.ConclusionsαS1‐casein‐sIgG4 plays a minor role in tolerance mechanisms in cases of CMA; humoral factors other than antigen‐sIgG4 may be involved.
Highlights
Immune response to cow's milk allergen (CMA) has been analyzed mostly using crude milk antigen or a mixture of various caseins
The present study analyzed the immunological changes during CM‐oral immunotherapy (OIT) using the PS‐basophil activation tests stimulated with αS1‐casein, an isolated CM allergen component
In accordance with previous studies that used fresh basophils and crude CM antigen, PS‐basophil activation stimulated with αS1‐casein consecutively decreased during the course of OIT. Both αS1‐casein‐specific IgE (sIgE) (Table 1) and PS‐basophil activation were reduced after OIT (Figure 1), and basophil activation was correlated with αS1‐casein‐sIgE (Table S3)
Summary
Immune response to cow's milk allergen (CMA) has been analyzed mostly using crude milk antigen or a mixture of various caseins. 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. Specific IgG4 (sIgG4) to αS1‐casein was detected in most of the pre‐OIT sera, which was not significantly increased after OIT. The addition of post‐OIT or tolerant serum to pre‐OIT serum significantly suppressed the basophil activation. The effect of oral immunotherapy (OIT) has been reported in the patients with immunoglobulin E (IgE)‐mediated cow's milk allergy (CMA).[2,3]. The estimated factors involved in the mechanism of desensitization include decreased allergen‐specific IgE (sIgE) and increased specific IgG4 (sIgG4), induction of regulatory T cells, and suppression of mast cells/basophils activation. Each casein component should have independent allergenic activities, because the amino acid sequence varies between casein fractions.[8,9]
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