Imbalance of Circulating B‐Cell Subsets Was Associated With Higher Risk of Relapses in RRMS Patients

Abstract

Objectives B‐cell aggregates below the meninges have been associated with progression of neurodegeneration in multiple sclerosis (MS). We aimed to investigate the frequency of different B‐cell subsets and their relationship with MS severity. Also, we quantified the CXCL13 and neurofilament (NfL) plasma levels. Methods According to the differential expression of IgD, CD38, CD27, HLA‐DR, CD138, IL‐10, and IL‐17, the frequency of different circulating B‐cell (CD19+) subsets was evaluated using flow cytometry. Plasma levels of CXCL13 and NfL were quantified using ELISA. Results Here, the severity of neurological impairment positively correlated with the percentage of plasmablast (CD138+, IL‐17+IL‐10−, HLA‐DR+IgD−) and memory CD27+CD38+B‐cell subsets (IL‐17+IL‐10− and HLA‐DR+IgD−), but negatively correlated with the proportion of HLA‐DR−IgD+ and IL‐17−IL‐10+ among transitional and plasmablasts. The occurrence of new clinical relapses was mainly observed among patients who showed an elevated proportion of CD138++ and HLA‐DR++IgD− plasmablast and HLA‐DR+IgD− memory and CD27+CD38+B‐cell subsets. Further, relapsed patients showed a higher percentage of IL‐17+IL‐10− cells among transitional, naïve and different memory B cells at baseline. By contrast, elevated frequency of HLA‐DR−IgD++ memory B cells and IL‐17−IL‐10+ among transitional and plasmablasts was observed in nonrelapsed patients over time. CXCL13 levels were higher in relapsed patients, and positively correlated with CD138+ plasmablasts and memory B‐cell subsets. Finally, plasma levels of NfL correlated positively with both CD138+ and HLA‐DR+IgD− plasmablasts, but negatively with transitional and naïve B cells with HLA‐DR−IgD+ phenotype. Conclusions In summary, our findings suggest that increased circulating anergic or immunogenic B‐cell subsets could be candidate biomarkers for low‐ and high‐risk of disease activity, respectively.