Unveiling biomarkers of telitacicept's efficacy in SLE treatment through proteomics and metabolomics

<h4>Background</h4>The pathogenesis of systemic lupus erythematosus (SLE) is closely associated with abnormal activation of B lymphocytes. Telitacicept simultaneously blocks B-cell stimulating factors and proliferation-inducing ligands, thereby inhibiting B-cell proliferation and differentiation, demonstrating favorable therapeutic efficacy in the majority of SLE patients. However, there is a lack of reliable biomarkers of efficacy and systematic elucidation of its mechanism of action.<h4>Methods</h4>The study employed proteomics and metabolomics analysis to explore biomarkers and mechanisms underlying therapeutic response variability to Telitacicept in SLE patients. Twenty-five SLE patients were enrolled and divided into the responder group and non-responder group based on the SLE Response Index 4 to identify key proteins, metabolites, and mechanisms associated with treatment response.<h4>Results</h4>Proteomics results revealed XPNPEP3, SRSF5, SRSF6, WARS1, IDH1, and ITLN1 as protein biomarkers correlated with Telitacicept efficacy in SLE patients. Metabolomics results indicated that pyruvate was a potential metabolic biomarker for responder group, while gamma-aminobutyric acid (GABA) was a potential biomarker for non-responder group. The combined analysis revealed that both pyruvate and IDH1 participate in the citric acid cycle. GABA showed a negative correlation with XPNPEP3.<h4>Conclusions</h4>The above results reveal biomarkers related to the differential efficacy of Telitacicept in treating SLE patients and potential mechanisms underlying these differences, which may provide a reference for personalized treatment and mechanistic research in SLE.