Abstract
Mechanisms of maintenance of immunological memory in the chronic course of seasonal allergic rhinitis remain poorly understood. The detailed understanding of these mechanisms is required for design of new approaches for allergy treatment. It is known that the level of allergen-specific IgE antibodies (sIgE), which play a key role in the development of the disease, is increased in patients with seasonal allergic rhinitis during pollination season. This study aimed to investigate the dynamics of serum IgE levels and characteristics of the clonal repertoire of IgE-secreting lymphocytes depending on the intensity of the patient's contact with the allergen. For three patients, allergic to birch pollen (22, 22, and 28 y.o.), we measured total IgE and birch pollen specific IgE levels at 6 time points with 2 week interval during the birch pollination season. Immunoglobulin heavy chain gene (IGH) clonal repertoire data for several B-cell subpopulations at different time points were obtained for one patient. We observe growth of the sIgE level (91%, 37%, and 64% compared to the baseline) at the peak of pollination season in all three donors. Initial increase in sIgE and IgE levels coincides with the birch pollination initiation; sIgE and total IgE levels correlate with the birch pollen air level (sIgE: R2 = 0.98 at p < 0.05; total IgE: R2 = 0.95 at p < 0.05). We detected IgE clonotypes only in samples obtained during the birch pollination, which indicates an increase of IGE-expressing cells concentration during this period. The frequency of IgE clonotypes was extremely low compared to that of the clonotypes of other isotypes (IgE — 0.01%, IgM — 48.4%, IgD — 14%, IgG — 17.4%, IgA — 19.8%). Hypermutation and phylogenetic analysis of the sequences from the 13 detected IgE-containing clonal groups showed that these IgE clonotypes could originate from IgG as a result of sequential isotype-switching.
Highlights
Seasonal allergic rhinoconjunctivitis (SAR), or seasonal allergic rhinitis, is one of the most common allergies
In order to characterize the seasonal dynamics of total IgE and specific IgE antibodies (sIgE) in serum we considered these levels with regards to the initial level of total IgE and sIgE, measured before the birch pollination season had started
Compared to the previously published study, we monitored the level of antibodies in serum at a higher temporal resolution, which allowed to demonstrate that level of sIgE starts to increase at the same time with the increase of birch pollen in air for patients with seasonal birch pollen allergy
Summary
Seasonal allergic rhinoconjunctivitis (SAR), or seasonal allergic rhinitis, is one of the most common allergies. While the most widely used therapeutic agents only aim to alleviate the symptoms (antihistamine and glucocorticosteroid drugs, mast cell membrane stabilizers), allergen-specific immunotherapy is the only currently practiced approach to SAR treatment that is designed to bring a long-term change in the chronic course of the disease. This is a long-term therapy that requires strict patient compliance and yields complete disappearance of the symptoms only in some patients [3]. We aimed to characterize the subpopulation of IgE-secreting plasmablast and plasma cells aand describe their relationship to other isotypes and memory B-cell population during seasonal exacerbation of the disease
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