Is intrathecal anti-CD20 an option to target compartmentalized CNS inflammation in progressive MS?

Abstract

B cells have gained enormous attention in the treatment of multiple sclerosis (MS). While our earlier pathogenic understanding of its cause primarily focused on B cell–derived plasma cells producing self-reactive antibodies, more recent findings support the theory that B cells themselves substantially contribute to MS pathogenesis. This conceptual change was primarily triggered by the empirical observation that anti-CD20–mediated B-cell depletion is effective in the treatment of relapsing-remitting MS (RRMS). Clearly exceeding the initial expectations, IV rituximab led to a rapid and lasting halt in the formation of new CNS lesions in patients with RRMS.1 Its further humanized successor ocrelizumab,2 as well as the human anti-CD20 antibody ofatumumab,3 confirmed these encouraging findings. The clinical efficacy of anti-CD20 provided greater appreciation of the fact that antigen-specific B cells are important antigen-presenting cells (APCs),4,5 most likely due to their unique capability to directly bind larger conformational antigens at very low concentrations via their B-cell receptor. Furthermore, B cells could be identified as a major source of proinflammatory cytokines,6 activating other APCs and fostering development of encephalitogenic T cells, jointly consolidating the concept that in RRMS, B cells exert distinctive pathogenic properties that can be targeted by systemic anti-CD20 treatment.