Research Article: B-cell subset changes and clinical predictors of telitacicept response in SLE patients with antiphospholipid antibody positivity: a prospective observational cohort study
Abstract:
To characterize the dynamic changes in B-cell subsets in Systemic lupus erythematosus (SLE) patients with antiphospholipid antibody (aPL) positivity treated with telitacicept and to identify baseline predictors of treatment response.
Twenty patients with active aPL-positive SLE receiving telitacicept in addition to standard therapy were enrolled, and 20 healthy individuals served as controls. Peripheral blood B-cell subsets and clinical parameters were assessed at baseline, week 12 and week 24. B cell subsets were analyzed using flow cytometry. Multivariable logistic regression was used to identify baseline predictors of SRI-4 response at week 24.
At baseline, the proportions of double-negative (DN) B cells and plasmablasts among total B cells were significantly higher in patients with aPL-positive SLE than in healthy controls (both p < 0.001). During the treatment of telitacicept, DN B-cell proportions decreased significantly by week 12 and continued to decline over 24 weeks, while plasmablast proportions decreased significantly by week 24; absolute counts of both subsets did not change significantly but showed a downward trend. Levels of BAFF, APRIL, IFN-?, IL-21 and IL-10 were significantly higher in patients with aPL-positive SLE than in healthy controls and decreased after 24 weeks of telitacicept treatment. At week 24, 65% (13/20) of patients achieved an SRI-4 response, with significant reductions in SLEDAI-2K scores, IgG, anti-double-stranded DNA (anti-dsDNA), and 24-h urine protein, along with increased complement C3 levels. Levels of aCL IgG ( p < 0.001), anti-? 2 GPI IgG ( p = 0.023), and LAC ( p = 0.025) were all reduced. Multivariable analysis showed that higher baseline IgG [OR = 1.95, 95% CI 1.05–3.63, P = 0.035] and anti-?2GPI IgG levels [OR = 1.06, 95% CI 1.01–1.12, P = 0.048] were independently associated with SRI-4 response at week 24.
Telitacicept may represent a safe and effective therapeutic option for patients with aPL-positive SLE, potentially exerting its therapeutic effects by influencing B-cell subsets, particularly DN B cells and plasmablasts. Elevated baseline IgG and anti-?2GPI IgG levels may predict a favorable response to telitacicept, and help identify patients who are more likely to benefit from this treatment.
Introduction:
SLE is a chronic autoimmune disease in which the immune system attacks healthy tissues and cells ( 1 , 2 ). aPL are the characteristic serological marker of antiphospholipid syndrome (APS), a systemic autoimmune disorder characterized by recurrent vascular thrombosis and pregnancy morbidity ( 3 ). Notably, aPL are also detected in a substantial proportion of patients with SLE, and their presence is linked with thrombotic risk and adverse pregnancy outcomes ( 4 ). Increasing evidence suggests that B cell…
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