Early decrease of T-bet⁺ B cells during subcutaneous belimumab predicts response to therapy in systemic lupus...

Systemic lupus erythematosus (SLE) is characterized by B cell dysregulation and expansion of atypical B cells that may correlate with disease manifestations and activity. This study investigated the impact of subcutaneous (sc) Belimumab (BLM) on the peripheral B cell compartment and on the functional properties of CD21^low, T-bet⁺ and CD11c⁺ atypical B cells, in 21 active SLE patients over a 12-month period. At baseline, active SLE patients displayed reduced unswitched IgM memory B cells and expansion of atypical B cells, compared to healthy donors and to SLE patients in remission. sc BLM therapy promptly restored B cell homeostasis with a reduction of T-bet⁺ B cells, observed early in patients responsive to therapy. These findings highlight the pathogenic role of T-bet⁺ B cells in SLE disease and suggest their potential utility as biomarker of clinical response.