CyTOF analysis of immune characteristics in cSLE: belimumab treatment and refractory cases.

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. Some patients still develop severe refractory SLE despite conventional treatments. Belimumab, a biologic targeting B lymphocyte stimulator (BLyS), shows therapeutic promise in SLE, but its effects on pediatric patients remain unclear. Methods: This study used CyTOF to analyze immunophenotypic changes before and after belimumab treatment and investigate immune features in refractory SLE. Results: Results showed that belimumab treatment primarily reduced transitional and naïve B cells, and also decreased age-associated B cells (ABCs), a subset implicated in autoimmunity or chronic inflammation. Plasma cells and plasmablasts persisted in refractory cases. CD38 expression on B cells was elevated in severe disease and correlated with disease activity, while CD73 expression increased during recovery and inversely correlated with activity. Discussion: These findings indicate that combining belimumab with conventional therapy induces significant immune modulation, particularly within B cells. Persistent plasma cells and plasmablasts may contribute to disease refractoriness. CD38 and the CD73-mediated adenosine pathway may provide insights for future research strategies in SLE.