B-cell Subset Changes and Predictors of Telitacicept Response in aPL-Positive SLE

Overview

This prospective study evaluated telitacicept treatment in 20 patients with active antiphospholipid antibody-positive systemic lupus erythematosus (aPL-positive SLE). Telitacicept significantly reduced pathogenic B-cell subsets and disease activity markers, with 65% achieving clinical response at 24 weeks. Baseline IgG and anti-β2GPI IgG levels predicted treatment response.

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease often complicated by antiphospholipid antibodies (aPL), which increase thrombotic risk. B cell dysregulation contributes to both SLE pathogenesis and aPL production. Current therapies have limitations in efficacy and safety, prompting investigation of novel agents like telitacicept, a fusion protein targeting BLyS and APRIL to modulate B cell function. Understanding B cell subset dynamics and predictors of response may optimize treatment strategies in aPL-positive SLE.

Data Highlights

Key Findings

• Patients with aPL-positive SLE had significantly higher baseline proportions of double-negative B cells and plasmablasts compared to healthy controls.
• Telitacicept treatment significantly decreased DN B cell proportions by week 12 and plasmablast proportions by week 24.
• Proinflammatory cytokines and B cell survival factors (BAFF, APRIL, IFN-γ, IL-21, IL-10) were elevated at baseline and reduced after 24 weeks of treatment.
• At 24 weeks, 65% of patients achieved an SRI-4 clinical response with improvements in disease activity, autoantibody levels, and complement C3.
• Higher baseline IgG and anti-β2GPI IgG levels independently predicted favorable SRI-4 response to telitacicept.

Clinical Implications

Telitacicept shows promise as an effective and safe adjunct therapy for active aPL-positive SLE by modulating pathogenic B cell subsets and inflammatory mediators. Baseline measurement of IgG and anti-β2GPI IgG can help identify patients most likely to benefit from telitacicept, enabling personalized treatment approaches. Monitoring B cell subset dynamics may also guide therapeutic decisions.

Conclusion

Telitacicept effectively reduces pathogenic B cell subsets and disease activity in aPL-positive SLE patients, with baseline IgG and anti-β2GPI IgG levels serving as predictors of clinical response. These findings support telitacicept as a valuable therapeutic option in this patient population.

References

1. Qingdao Municipal Hospital Rheumatology Department Study 2022-2025 -- Alterations in B-cell Subsets and Clinical Predictors of Response to Telitacicept in Antiphospholipid Antibody-Positive SLE Patients