Single‐Cell Immune Profiling Reveals Neutrophils Promote Myasthenia Gravis Exacerbation Through BAFF Secretion

Abstract Neutrophils play a critical role in the pathogenesis of autoimmune diseases, including myasthenia gravis (MG), but their specific function in MG exacerbations remains unclear. This study utilizes single‐cell RNA sequencing (scRNA‐seq) of bone marrow and peripheral blood from MG patients during acute exacerbations, combined with experimental autoimmune myasthenia gravis (EAMG) mouse models and clinical cohort analyses, to investigate the potential involvement of a neutrophil–B‐cell activating factor (BAFF) –plasma cell axis. The results reveal that, during MG acute exacerbation, bone‐marrow neutrophils exhibit significantly enhanced maturation. Upon migration to the peripheral blood, these neutrophils secrete increased amounts of BAFF, further promoting pathological B‐cell differentiation and plasma cell activation. Moreover, gene knockout models and serum cytokine analyses reveal that the IFN‐γ signaling pathway is a key driver of this excessive BAFF secretion, supporting the existence of a neutrophil–BAFF–plasma cell interaction relevant to MG exacerbation. Clinical data analysis shows that MG patients with high baseline neutrophil levels derive greater benefit from treatment with the BAFF/APRIL dual‐target inhibitor telitacicept. Collectively, this study reveals the mechanistic link between neutrophil activation and MG exacerbation, providing insights that may inform precision‐targeted immunotherapy.