Soluble IFNAR1 is linked to systemic and patient-reported outcomes, and emerges as a potential key regulator and predictive biomarker in Sjögren’s disease 3522

Abstract Description Objectives Leflunomide and hydroxychloroquine (LEF-HCQ) show promise in treating Sjögren’s disease. To better understand treatment mechanisms and patient variability, we analyzed serum proteomic profiles of healthy individuals (HCs) and Sjögren’s disease (SjD) patients, aiming to identify key differences between non-responders (NR) and responders (R) and uncover biomarkers predictive of therapeutic outcomes. Methods Using Olink Explore we quantified 2,926 proteins in serum samples from 28 SjD patients (10 NR, 11 R, 7 placebo) at baseline and after 24 weeks, along with 22 HCs. Using PLS-DA, we identified 10 distinct protein groups that effectively separated HCs, NRs, and Rs. We further analyzed the evolution of these proteins to understand how LEF-HCQ influences disease progression. Results Protein clusters revealed a pronounced inflammatory profile in pSD patients, with differential expression patterns distinguishing NRs from Rs. Soluble (s) IFNAR1 was significantly downregulated in SjD patients compared to HCs. Notably, lower baseline sIFNAR1 levels predicted a more robust response to treatment. In response to LEF-HCQ, sIFNAR1 levels increased, correlating strongly with improved clinical scores (ESSDAI, ESSPRI, STAR). Conclusions Our data underscore sIFNAR1’s dual role in predicting treatment efficacy and monitoring therapeutic response, highlighting its importance in disease pathophysiology and potential for guiding personalized treatment strategies in Sjögren’s disease. Funding Sources AbbVie funded this study and participated in the interpretation of data, reviewing, and approval of the publication. No honoraria or payments were made for authorship. Topic Categories Therapeutic Approaches to Autoimmunity (THER)