This study shows that GOS/FOS supplementation induces a beneficial antibody profile. GOS/FOS reduces the total Ig response and modulates the immune response towards CMP, while leaving the response to vaccination intact. This suggests that oral GOS/FOS supplementation is a safe method to restrain the atopic march.

Background Peanut oral immunotherapy (PNOIT) induces persistent tolerance to peanut in a subset of patients and induces specific antibodies which may play a role in clinical protection. The contribution of induced antibody clones to clinical tolerance in PNOIT is unknown, however. Objective We hypothesized that PNOIT induces a clonal, allergen-specific B cell response, which could serve as a surrogate for clinical outcomes. Methods We used a fluorescent Ara h 2 multimer for affinity-selection of Ara h 2-specific B cells, and subsequent single cell immunoglobulin amplification. Diversity of related clones was evaluated by next-generation sequencing (NGS) of immunoglobulin heavy chains from circulating memory B cells using 2×250 paired-end sequencing on the Illumina MiSeq platform. Results Expression of class-switched antibodies from Ara h 2 positive cells confirms enrichment for Ara h 2 specificity. PNOIT induces an early and transient expansion of circulating Ara h 2 specific memory B cells that peaks at week 7. Ara h 2-specific sequences from memory cells have rates of non-silent mutations consistent with affinity maturation. The repertoire of Ara h 2-specific antibodies is oligoclonal. NGS-based repertoire analysis of circulating memory B cells, reveals evidence for convergent selection of related sequences in 3 unrelated subjects, suggesting the presence of similar Ara h 2-specific B cell clones. Conclusions Using a novel affinity selection approach to identify antigen-specific B cells, we demonstrate that the early PNOIT induced Ara h 2-specific BCR repertoire is oligoclonal, somatically hypermutated and shares similar clonal groups among unrelated individuals consistent with convergent selection.

Maintenance of tolerance to cow's milk in atopic children and adults without CMA is associated with elevated levels of specific IgG4, in combination with low specific IgE. The up-regulation of specific IgG4 in tolerant atopic individuals may be related to the type of allergen and its regular dose of exposure.

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