Lupus science & medicine · 2026
B-cell landscape remodelling following dual BAFF/APRIL inhibition with telitacicept in lupus nephritis: extrafollicular axis clearance and its association with clinical response.
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Yi Wenqian, Tang Xiaojun, Wei Hua, Wu Juan, Jiang Xiaoman, Yang Zirui, Jia Jieting, Han Tao, Huang Saisai, Ma Xiaolei, Jin Zi-Yi, Zhang Qingfeng, Zhu Yun, Feng Xuebing, Sun Lingyun
Аннотация
OBJECTIVE: The therapeutic efficacy of telitacicept, a novel dual BAFF/APRIL inhibitor in active lupus nephritis (LN) requires further characterisation. This prospective cohort study characterised the B-cell landscape changes in patients with LN receiving telitacicept with a small belimumab-treated reference group.
METHODS: Patients with active LN received telitacicept (n=19) or belimumab (n=5) for 24 weeks alongside standard therapy. Peripheral B-cell subsets were analysed at baseline, week 4, 12 and 24 using full-spectrum flow cytometry. The primary endpoint was the proportion of patients achieving primary efficacy renal response (PERR) at week 24.
RESULTS: After excluding 3 dropouts, 16 telitacicept and 5 belimumab were included in the final analysis. In the telitacicept group, 43.8% and 62.5% of patients achieved PERR at week 4 and week 24, respectively, showing a progressive increasing trend alongside the belimumab reference group. Telitacicept was associated with numerically greater reductions in 24-hour urine protein and anti-double-stranded DNA titres, alongside serological improvements relative to the belimumab arm. While both treatments contracted the naïve B-cell pool, telitacicept uniquely induced more profound and sustained depletion of the pathogenic extrafollicular axis. Specifically, plasmablasts and mature plasma cells were effectively eradicated in the telitacicept group, whereas these subsets remained largely refractory to belimumab. This comprehensive ablation resulted in a significant relative enrichment of switched memory B-cells, which negatively correlated with disease activity, suggesting a passive reshaping of the residual B-cell pool rather than an active immune reset. Notably, early reductions in naïve B-cells (area under the curve (AUC)=0.909), mature plasma cells (AUC=0.964) and plasmablasts (AUC=0.836) were identified as early immunological correlates of sustained renal response.
CONCLUSION: Telitacicept was associated with numerically greater clinical and immunological remission by targeting the naïve-extrafollicular axis that evades single BAFF inhibition. Early depletion of plasma cells and naïve B-cells serves as promising molecular indicators associated with achieving sustained renal remission.
TRIAL REGISTRATION NUMBER: NCT05588830.
METHODS: Patients with active LN received telitacicept (n=19) or belimumab (n=5) for 24 weeks alongside standard therapy. Peripheral B-cell subsets were analysed at baseline, week 4, 12 and 24 using full-spectrum flow cytometry. The primary endpoint was the proportion of patients achieving primary efficacy renal response (PERR) at week 24.
RESULTS: After excluding 3 dropouts, 16 telitacicept and 5 belimumab were included in the final analysis. In the telitacicept group, 43.8% and 62.5% of patients achieved PERR at week 4 and week 24, respectively, showing a progressive increasing trend alongside the belimumab reference group. Telitacicept was associated with numerically greater reductions in 24-hour urine protein and anti-double-stranded DNA titres, alongside serological improvements relative to the belimumab arm. While both treatments contracted the naïve B-cell pool, telitacicept uniquely induced more profound and sustained depletion of the pathogenic extrafollicular axis. Specifically, plasmablasts and mature plasma cells were effectively eradicated in the telitacicept group, whereas these subsets remained largely refractory to belimumab. This comprehensive ablation resulted in a significant relative enrichment of switched memory B-cells, which negatively correlated with disease activity, suggesting a passive reshaping of the residual B-cell pool rather than an active immune reset. Notably, early reductions in naïve B-cells (area under the curve (AUC)=0.909), mature plasma cells (AUC=0.964) and plasmablasts (AUC=0.836) were identified as early immunological correlates of sustained renal response.
CONCLUSION: Telitacicept was associated with numerically greater clinical and immunological remission by targeting the naïve-extrafollicular axis that evades single BAFF inhibition. Early depletion of plasma cells and naïve B-cells serves as promising molecular indicators associated with achieving sustained renal remission.
TRIAL REGISTRATION NUMBER: NCT05588830.