B-cell centrality dictates therapeutic efficacy across autoimmune diseases: a systematic review

Background B cells play a critical role in autoimmunity through autoantibody production, plasma cell differentiation, antigen presentation, cytokine secretion, and germinal center responses. The clinical efficacy, durability, and safety profiles vary across autoimmune diseases. Therefore, the objective is to assess B-cell therapeutic responses and their correlation with disease pathology in autoimmunity. Methods Embase, Web of Science, and PubMed were systematically screened for clinical trials published between 2020 and July 2025. A total of 24 clinical trials across five autoimmune conditions—pemphigus vulgaris, myasthenia gravis, rheumatoid arthritis, systemic sclerosis, and Sjögren’s syndrome—were evaluated for B-cell-targeted therapy. Interventions included B-cell depletion therapy, CAR-T cell therapy, BTK inhibition, rituximab and its biosimilars, and combination strategies. Results Across 24 clinical trials, more than 3,500 participants were included. We observed that autoantibody-mediated diseases pemphigus vulgaris and myasthenia gravis had the most superior and durable immune response to B-cell depletion by rituximab and inebilizumab, respectively. BTK inhibition showed rapid but non-durable responses. Immune complex diseases like rheumatoid arthritis and systemic sclerosis showed improvement in activity scores and partial response, and no clinical remission after treatment with rituximab and its biosimilars. The next-generation approach BCMA-directed CAR T-cell therapy showed promising results with potential durability in myasthenia gravis. Combination therapy using belimumab and rituximab resulted in a significantly better clinical outcome than monotherapy in Sjögren’s syndrome. Overall, B-cell therapy safety profiles showed no severe adversity and were well tolerated. Conclusions The success of B-cell therapeutics appears to align with B-cell contribution, disease biology, and the depth of B-cell targeting in autoimmune conditions. Precision targeting is needed to effectively combat autoimmune diseases.