Type II interferon-associated proteins in Sjogren’s disease: potential novel indicators for disease monitoring and predicting response to leflunomide and hydroxychloroquine therapy 3517

Abstract Description Introduction Challenges in primary Sjogren’s disease (pSD) include a lack of reliable biomarkers, unelucidated pathogenesis, and no standard treatment. The RepurpSS-I trial showed 4.4-point ESSDAI improvement with leflunomide/hydroxychloroquine (LEF/HCQ) therapy. We aimed to identify biomarkers predictive of clinical response and disease activity, and to explore pathogenic pathways. Methods Serum proteome (Olink Immuno-oncology panel, 92 proteins) of 28 pSD patients and 8 healthy controls (HC) of the RepurpSS-I trial was analyzed at baseline and after 24 weeks of LEF/HCQ. Proteomic changes were correlated to clinical endpoints. Transcriptome data of blood mononuclear cells and monocytes were used to assess type I and II interferon (IFN) scores. Results At baseline, 29 proteins were differentially expressed in pSD vs. HC. LEF/HCQ downregulated 22 of 27 upregulated proteins. Fourteen baseline proteins and changes in CXCL11, CXCL10, TNF-α, CD70 correlated with clinical response. Principal component analysis showed an IFN-γ-associated protein set, with baseline CXCL10 and CXCL11 distinguishing responders from non-responders by ESSDAI, and HC. Distinct type II IFN imprinting was found in monocytes and associated with disease activity changes. Conclusion Our data indicate a significant role for a type II IFN-associated immune response in pSD that is targeted by LEF/HCQ. Type II IFN-associated proteins hold potential to monitor disease activity and to predict treatment response. Funding Sources ZonMW, ReumaNederland Topic Categories Translational and Interventional Immunology (TI)