Comparative analysis of the B cell receptor repertoire during relapse and remission in patients with multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic, multifactorial, inflammatory and demyelinating disease of the central nervous system (CNS), which involves an autoimmune response against components of the myelin sheaths. Anti-B cell therapies have been proven to be successful in reducing relapses. Therefore, the study of B cells in both phases of the disease (relapse and remission) is of great importance. Here, we analyzed peripheral blood-cell BCR repertoire from 11 MS patients during a relapse phase and during remission, 6 patients with other inflammatory neurological diseases (OIND) and 10 healthy subjects (HCs), using next generation sequencing. In addition, immunoglobulins G, M, A and D were quantified in the serum of patients and controls, using ELISA. BCR repertoire of relapsing MS patients showed lower diversity, as well as a higher rate of somatic hypermutation compared to the other study groups. Within this group, the highest percentage of shared clonotypes was observed. IGHV4–32 gene was identified as a potential differential biomarker between MS and OIND, as well as IGL3–21 gene as a potential MS biomarker. On the other hand, an elevation of IgG and IgD was found in the serum of MS patients during remission, and the serum IgG was also elevated in MS patients during relapse. In conclusion, these results show the important role of B cells in the pathogenesis of the MS relapses and a new panorama on the analysis of the peripheral blood BCR repertoire to obtain diagnostic tools for MS. Furthermore, this work highlights the need of studies in diverse populations, since results reported in Caucasian populations may not coincide with the immunological course of MS patients in other latitudes, due to differences in genetic background and environmental exposures.