Beyond B Cell Depletion: Adhesion and Activation Network Remodeling During Repeated Intravenous Anti-CD20 Therapy in Multiple Sclerosis

INTRODUCTION: Immune cell depletion with anti-CD20 monoclonal antibodies (mAbs) is an effective disease-modifying therapy in multiple sclerosis (MS). CD20 is mainly specific to the B cell lineage and is lost upon differentiation into plasma cells. Here, we aimed to elucidate the consequences of intravenous CD20 depletion every 6 months on the expression of adhesion molecules and activation networks of peripheral immune cell subsets. METHODS: In this exploratory study, we investigated 15 people with MS (pwMS) treated with either rituximab (RTX, n=7) or ocrelizumab (OCR, n=8), with examinations scheduled before treatment initiation and every 12 weeks for up to 15 months. Phenotyping of immune cell surface molecules for adhesion and activation in peripheral blood was performed by multi-parametric fluorescence cytometry. RESULTS: T cells showed reduced activation and decreased expression of effector markers, consistent with secondary T cell deactivation. Most changes became apparent after at least two treatment cycles. Taking the limited sample size into consideration, we observed no significant differences in the expression kinetics of these surface markers between the RTX- and OCR-treated groups. CONCLUSION: Profiling of surrogate markers of cell adhesion and activation in peripheral immune cell subsets in pwMS indicates that anti-CD20 treatment leads to a disruption of B cell-dependent immune networks. Although OCR and RTX bind to distinct sites and use distinct mechanisms, their effects were indistinguishable. Furthermore, the plateau in expression dynamics observed after two cycles warrants further investigation.