Abstract
Multiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system, still represents one of the most common causes of persisting disability with an early disease onset. Growing evidence suggests B cells to play a crucial role in its pathogenesis and progression. Over the last decades, monoclonal antibodies (mabs) against the surface protein CD20 have been intensively studied as a B cell targeting therapy in relapsing MS (RMS) as well as primary progressive MS (PPMS). Pivotal studies on anti-CD20 therapy in RMS showed remarkable clinical and radiological effects, especially on acute inflammation and relapse biology. These results paved the way for further research on the implication of B cells in the pathogenesis of MS. Besides controlling relapse development in RMS, ocrelizumab (OCR) also showed clinical benefits in patients with PPMS and became the first approved drug for this disease course. In this review, we provide an overview of the current anti-CD20 mabs used or tested for the treatment of MS—namely rituximab (RTX), OCR, ofatumumab (OFA), and ublituximab (UB). Besides their effectiveness, we also discuss possible limitations and safety concerns especially in regard to long-term treatment, both for this class of drugs overall as well as for each anti-CD20 mab individually. Additionally, we elucidate to what extent anti-CD20 therapy may alter the function of other immune cells, both directly or indirectly. Finally, we cover the current knowledge on repopulation of CD20+ cells after cessation of anti-CD20 treatment and discuss future aspirations towards alternative, further developed B cell silencing therapies.
Highlights
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS)
The most common early course is relapsing–remitting MS (RRMS), which is characterized by intermittent exacerbations that are followed by periods of complete or partial recovery
Studies indicate that the anti-inflammatory cytokine IL-10 is predominantly produced by naïve B cells, while tumor necrosis factor α (TNFα) and LT are largely produced by differentiated memory B cells [6, 12]
Summary
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Studies demonstrate that B cells of patients diagnosed with MS are chronically activated and show an alteration of their cytokine profile They are matured in a pro-inflammatory manner resulting in a higher production of IL-6 compared to B cells of healthy individuals [6,7,8]. Studies indicate that the anti-inflammatory cytokine IL-10 is predominantly produced by naïve B cells, while TNFα and LT are largely produced by differentiated memory B cells [6, 12]. This observation is most likely context dependent [12].
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