Multiple Sclerosis Is Associated with Immunoglobulin Germline Gene Variation of Transitional B Cells

Abstract

The regulatory functions of the B-cell compartment play an important role in the development and suppression of the immune response. Disruption of their anti-inflammatory functions may lead to the acceleration of immunopathological processes, and to autoimmune diseases, in particular. Unfortunately, the exact mechanism underlying the functioning and development of regulatory B cells (Breg) has not yet been fully elucidated. Almost nothing is known about their specificity and the structure of their B-cell receptors (BCRs). In this research, we analyzed the BCR repertoire of the transitional Breg (tBreg) subpopulation with the CD19+CD24highCD38high phenotype in patients with multiple sclerosis (MS), using next-generation sequencing (NGS). We show, for the first time, that the immunoglobulin germline distribution in the tBreg subpopulation is different between MS patients and healthy donors. The registered variation was more significant in patients with a more severe form of the disease, highly active MS (HAMS), compared to those with benign MS (BMS). Our data suggest that during MS development, deviations in the immunoglobulin Breg repertoire occur already at the early stage of B-cell maturation, namely at the stage of tBregs: between immature B cells in the bone marrow and mature peripheral B cells.

The Level of Anti-Viral Antigen-Specific Antibodies to EBNA-1 in the Serum of MS Patients Does not Depend on the Severity of the Disease

“…The amount of antigen-specific antibodies to EBNA-1 (386–405 aa) in the blood sera of patients with MS and healthy donors (HD) was determined by enzyme-linked immunosorbent assay (ELISA). In this work, we consider two clinical variants of the course of relapsing–remitting MS—benign MS (BMS) and a more aggressive one, highly active MS (HAMS) [ 8 , 9 ]. BMS is characterized by a slow progression in the absence of specific treatment and a relatively low Kurtzke Expanded Disability Status Scale (EDSS) score, less than 4.…”

“…The study of the titer of antibodies to viral antigens in patients with MS will help understand how the level of activation of the immune system in response to EBV is associated with the severity of MS. Thus, the purpose of our study was to determine the level of antiviral antibodies to EBNA-1 (386–405 aa) in the blood of patients with aggressive MS (highly active MS (HAMS)) and a less severe form of the disease, benign MS (BMS) [ 8 , 9 ].…”

Cell-Mediated Immunity in Multiple Sclerosis Patients Who Discontinued Therapy with an Integrin Inhibitor

“…Ломакин и соавт. проанализировали репертуар B-клеточных рецепторов регуляторных В-клеток ПК больных с РС и обнаружили, что частота встречаемости ряда генов регуляторных В-клеток отличалась от распределения генов иммуноглобулинов у здоровых лиц, причём этот сдвиг был более выражен у пациентов с высокоактивным РС [24]. Полученные данные позволили авторам предположить, что изменение репертуара регуляторных В-клеток при РС происходит на ранних этапах созревания В-клеток.…”