Inflammatory cytokines and their potential role in Sjogren’s syndrome risk: insights from a mendelian randomization study

Abstract Aim This study aimed to investigate the causal impact of inflammatory cytokines on Sjogren’s Syndrome (SS) and to identify potential biomarkers for SS clinical management using Mendelian Randomization (MR). Materials and methods Leveraging GWAS summary data of inflammatory cytokines and SS, we executed the first two-sample MR analysis. Genetic variants from prior GWASs associated with circulating inflammatory cytokines served as instrumental variables (IVs). Data regarding cytokines were analyzed using the Olink Target-96 Inflammation panel, synthesizing data from 14,824 participants. GWAS summary statistics for SS were procured from the UK Biobank, focusing on samples of European ancestry. To discern the causal relationship between inflammatory cytokines and SS, several MR methodologies, including inverse variance weighted (IVW) and MR-Egger regression, were applied. Results After rigorous IV quality control, 91 cytokines were incorporated into the MR analysis. The IVW analysis identified 8 cytokines with a positive association to SS: Axin-1 (OR 2.56, 95% CI 1.07–6.10), T-cell surface glycoprotein CD5 (OR 1.81, 95% CI 1.08–3.02), CUDP1 (OR 1.61, 95% CI 1.00-2.58), CXCL10 (OR 1.92, 95% CI 1.25–2.95), IL-4 (OR 2.18, 95% CI 1.22–3.91), IL-7 (OR 2.35, 95% CI 1.27–4.33), MCP-2 (OR 1.27, 95% CI 1.05–1.54), and TNFRSF9 (OR 1.83, 95% CI 1.03–3.24), suggesting their potential in increasing SS risk. Conclusion Our study conducted through MR, identified various inflammatory cytokines associated with SS risk, validating some previous research results and offering some new potential biomarkers for SS. However, these findings necessitate further research for validation and exploration of their precise role in the onset and progression of SS.