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

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Systemic lupus erythematosus (SLE) involves B cell dysregulation and expansion of atypical B cells, linked to disease activity.
• Atypical B cells, including CD21^low, T-bet⁺, and CD11c⁺ subsets, are implicated in SLE pathogenesis.

Purpose of the Study:

• To investigate the therapeutic effect of subcutaneous Belimumab (BLM) on peripheral B cell populations in active SLE patients.
• To assess the impact of BLM on atypical B cell subsets (CD21^low, T-bet⁺, CD11c⁺) and their functional properties.

Main Methods:

• A 12-month study involving 21 active SLE patients receiving subcutaneous Belimumab (BLM).
• Analysis of peripheral B cell compartments, including unswitched IgM memory B cells and atypical B cell subsets.
• Comparison of B cell profiles at baseline, during therapy, and against healthy donors and SLE patients in remission.

Main Results:

• Active SLE patients exhibited reduced unswitched IgM memory B cells and expanded atypical B cells compared to controls.
• Subcutaneous Belimumab (BLM) therapy rapidly restored B cell homeostasis.
• A reduction in T-bet⁺ B cells was observed early in patients responding to BLM therapy.

Conclusions:

• T-bet⁺ B cells play a pathogenic role in Systemic Lupus Erythematosus (SLE).
• Subcutaneous Belimumab (BLM) effectively modulates B cell abnormalities in active SLE.
• T-bet⁺ B cells may serve as a valuable biomarker for predicting clinical response to Belimumab in SLE.