Briefly, depending on their B cell-depleting characteristics, anti-CD20 mAbs are grouped into type I and type II. Certain B cell-depleting characteristics of the anti-CD20 mAb (rituximab) used in these studies could be one of the reasons for the partial resistance of B cells found within the CNS of these patients. Intrathecal injection of rituximab in patients with low-inflammatory SPMS resulted in incomplete depletion of B cells within the cerebrospinal fluid compartment and insufficient dampening of neuroinflammation. Ĭlinical studies have demonstrated that B cells residing in these specific CNS compartments are protected from depletion following conventional anti-CD20 therapy. Despite these therapeutic developments, SPMS-in which one of the characteristic features is chronic CNS-compartmentalized inflammation-remains difficult to treat. Furthermore, in patients with primary progressive MS, ocrelizumab is associated with lower rates of clinical and magnetic resonance imaging progression compared with placebo. More recent studies involving humanized (ocrelizumab) and human (ofatumumab) anti-CD20 mAbs confirmed a high level of efficacy in RRMS in the clinic. In initial studies, depletion of circulating B cells by rituximab, a chimeric anti-CD20 monoclonal antibody (mAb), led to a rapid reduction in gadolinium-enhancing lesions and magnetic resonance imaging lesion load, as well as a decrease in relapse activity in patients with RRMS. The updated conceptual understanding of the involvement of B cells in the immunopathophysiology of MS has mainly emerged on the basis of the success of anti-CD20 therapy in treating patients with RRMS. Our results demonstrate the usefulness of anti-CD20 mAbs for the modulation of B cell-driven peripheral immune response and CNS pathology, with type II antibodies potentially being superior to type I in the depletion of tissue-infiltrating B cells. B cell depletion rates in the 18B12/B6 model were comparable with those observed in obinutuzumab-treated hCD20xhIgR3 mice. Additionally, obinutuzumab had beneficial effects on spinal cord myelination. Obinutuzumab and rituximab had an impact on splenic and CNS-infiltrated B cells with slightly differential depletion efficacy. Neither mAb affected clinical disease or serum antibody levels. While hCD20xhIgR3 mice were injected intravenously with an anti-human CD20 mAb (5 mg/kg) (rituximab (a type I anti-CD20 mAb) or obinutuzumab (a type II anti-CD20 mAb), B6 mice received the anti-mouse CD20 antibody 18B12. Male hCD20xhIgR3 mice and wild-type C57BL/6 (B6) mice were immunized with human myelin oligodendrocyte glycoprotein (MOG) 1–125 to induce EAE. This study aimed to determine the effects of a novel class of anti-CD20 mAbs on vascular and extravascular central nervous system (CNS)-infiltrating B cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Successful therapy with anti-CD20 monoclonal antibodies (mAbs) has reinforced the key role of B cells in the immunopathology of multiple sclerosis (MS).
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