Clonal differentiation of plasmablasts undergoing oral immunotherapy in patients with milk allergy

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Background: Anaphylaxis is a life threatening complication of allergy and one of the treatment approaches for allergy is immunotherapy. Allergen immunotherapy is the only treatment that can alter the natural history of allergic disease. Oral immunotherapy is a viable therapeutic route in patients with food allergies, during which peripheral plasmablasts, which are activated B cells, expand, and allergen-specific IgG4 is induced. We aimed to characterize the profile of plasmablasts undergoing oral immunotherapy.

Methods: A detailed profile of plasmablasts in 2 patients with milk allergies undergoing oral immunotherapy is provided by single cell analysis. The involvement of the subclasses and isotypes in plasmablasts in individuals undergoing oral immunotherapy was clarified by single-cell transcriptomics analysis and B cell immune receptor analysis and profile analysis of recombinant antibodies.

Results: Some clonally expanded antibodies and IgD clones were found to recognize allergens. Furthermore, constructing a clonal tree, over 80 % matched complementarity-determining region (CDR) clones were identified. Several IgA1 antibodies in the clonal trees were also found to recognize allergens.

Conclusions: Plasmablasts developed clonal differentiation in patients with milk allergy undergoing OIT. And somatic hypermutations and the allergen-positive rate of plasmablast are dependent on their subclasses and isotypes.