P158 Evaluating CD40L and CXCL13 as predictors of treatment response in systemic lupus erythematosus

Abstract Background/Aims Systemic lupus erythematosus (SLE) is a complex autoimmune disease marked by autoantibody production. Although rituximab, an anti-CD20 monoclonal antibody, failed to meet endpoints in two major trials, it has demonstrated benefit in open-label studies. However, treatment response remains variable, highlighting the need for predictive biomarkers. Currently, there are no validated tools to guide patient selection for anti-CD20 therapies. This study evaluates serum CXCL13 (a B cell chemoattractant) and soluble CD40L (a T cell-derived B cell activation signal), to determine their potential as biomarkers for predicting treatment response and enabling more precise therapeutic stratification in SLE. Methods Baseline serum samples were prospectively collected from 30 patients fulfilling the 2019 EULAR/ACR classification criteria for SLE with active disease (SLEDAI-2K ≥6 or BILAG 1A/2B score). Soluble CD40 ligand (sCD40L) and CXCL13 concentrations were quantified using commercially available ELISA kits. Patients were stratified into those receiving anti-CD20 therapy and those receiving other immunosuppressive regimens. Clinical response at 3-6 months was assessed using achievement of LLDAS, SRI-4, BICLA, and BILAG. Disease activity parameters (SLEDAI-2K, global BILAG score, and anti-dsDNA titres) were recorded at baseline and follow-up visit, and correlations with biomarker levels were examined. Baseline serum protein concentrations of CD40L and CXCL13 were evaluated in relation to clinical outcomes, and disease activity measures pre- and post-treatment, using the Mann-Whitney U test and Wilcoxon rank sum exact test. Results Of the 30 patients included, 19 received anti-CD20 therapies and 11 received other immunosuppressive regimens. CXCL13 serum concentration, but not CD40L concentration, demonstrated a significantly correlation with both SLEDAI-2K (p = 0.013) and Global BILAG scores (p = 0.007). Among patients treated with anti-CD20 therapies, serum CXCL13 concentration significantly decreased from baseline (median: 0.41pg/ml) to follow-up (median:0.22pg/ml) visit in those who responded to treatment (p = 0.002) but was not observed in non-responders. This decrease was consistent across multiple response measures (LLDAS, SRI-4, BICLA, and BILAG activity). In contrast, no such pattern was observed in responders receiving non-anti-CD20 therapies. Baseline CD40L serum concentrations (median R: 1pg/ml vs NR: 1.57pg/ml, p = 0.0268), and follow-up concentrations (median R: 1.1pg/ml vs NR: 1.6pg/ml, p = 0.034), were significantly lower in anti-CD20 therapy responders compared with non-responders, as assessed by LLDAS and BICLA, respectively. Again, this association was not evident among non-responders to anti-CD20 therapy. (R: responders, NR: non-responders). Conclusion Elevated baseline CD40L identified patients less likely to benefit from anti-CD20 B cell depletion, supporting its use for pre-treatment stratification. By contrast, CXCL13 was not predictive at baseline, but a significant on-treatment fall aligned with clinical response, making it a useful pharmacodynamic marker of target engagement in responders. Taken together, CD40L (who to treat) and CXCL13 dynamics (whether treatment is working) may provide complementary biomarkers to guide anti-CD20 therapy in SLE. Disclosure Y. Charavanamuttu: None. K. Labiba: None. F. Tariq: None. C. Wincup: Consultancies; Abbvie, Gilead. Honoraria; AstraZeneca, BMS, CSL Vifor, Kyverna, Otsuka, UCB. Grants/research support; Research Funding Paid to Institution – AstraZeneca, Versus Arthritis, Lupus UK, Lupus Foundation of America. Other; Advisory Board – Biogen; Support for Travel – AbbVie.