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

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.