Correlated dynamics of serum IGE and IGE+ clonotype count with allergen air level in seasonal allergic rhinitis

About authors

1 Skoltech, Moscow, Russia

2 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia

3 Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Ivan V. Zvyagin
Miklukho-Maklaya, 16/10, Moscow, 117997; moc.liamg@nigayvzi

About paper

Funding: the study was supported by the Grants Council under the President of the Russian Federation (grant MK6000.2018.4).

Acknowledgments: we are very grateful to all the donors who participated in the study.

Author contribution: Mikelov AI — antibody levels determination, IGH cDNA libraries preparation, sequencing data and results analysis, research design, drafting; Staroverov DB — cell subpopulations isolation (flow cytofluorometry); Komech EA — blood samples collection, cell subpopulations isolation (flow cytofluorometry); Lebedev YB — results analysis and discussion, advisory support; Chudakov DM — results analysis and discussion, advisory support (cDNA libraries preparation); Zvyagin IV — IGH cDNA libraries preparation,sequencing data and results analysis, research design, drafting, research organization.

Received: 2019-10-09 Accepted: 2019-10-23 Published online: 2019-10-31

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.

Keywords: allergic rhinitis, allergen-specific IgE, birch pollen, seasonal dynamics, immunoglobulin clonal repertoire