Ocrelizumab associates with reduced cerebrospinal fluid B and CD20 CD4 T cells in primary progressive multiple sclerosis.

The anti-CD20 monoclonal antibody ocrelizumab reduces disability progression in primary progressive multiple sclerosis. CD20 is a prototypical B-cell marker; however, subpopulations of CD4 and CD8 T cells in peripheral blood and cerebrospinal fluid also express low levels of CD20 (CD20). Therefore, direct targeting and depletion of these CD20 T-cell subpopulations may contribute to the therapeutic effect of ocrelizumab. The aim of this observational cohort study was to compare CD20 B-cell and CD20 T-cell distributions between peripheral blood and cerebrospinal fluid of ocrelizumab-treated or ocrelizumab-untreated people with primary progressive multiple sclerosis. Ocrelizumab treatment was associated with depletion of circulating B cells and CD20 CD4 and CD20 CD8 T cells ( < 0.0001, = 0.0016 and = 0.0008, respectively) but, in cerebrospinal fluid, only with lower proportions of B cells and CD20 memory CD4 T cells ( < 0.0001 and = 0.0043, respectively). The proportional prevalence of cerebrospinal fluid CD20 memory CD8 T cells was not significantly reduced ( = 0.1333). Only in cerebrospinal fluid, the proportions of CD20 cells within CD4 and not CD8 T cells positive for CCR5, CCR6 and CXCR3 were reduced in ocrelizumab-treated participants. The proportion of CD20 CD4 T cells and abundance of CD4 relative to CD8 T cells in cerebrospinal fluid correlated positively with age ( = 0.6799, = 0.0150) and Age-Related Multiple Sclerosis Severity score ( = 0.8087, = 0.0014), respectively. We conclude that, in contrast to cerebrospinal fluid CD20 CD8 T cells, B cells and CD20 CD4 T cells are reduced in cerebrospinal fluid of people with primary progressive multiple sclerosis with an ocrelizumab-associated depletion of circulating B cells and CD20 T cells. Therefore, these cells are likely to contribute to the therapeutic effects of ocrelizumab in people with primary progressive multiple sclerosis.