{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:14:06Z","timestamp":1791591246826,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"Objective<\/jats:title>Primary Sj\u00f6gren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS.<\/jats:p><\/jats:sec>Methods<\/jats:title>We analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n\u00a0=\u00a0462 patients). We determined circulating interferon\u2010\u03b1 (IFN\u03b1) and IFN\u03b3 protein concentrations using digital single molecular arrays (Simoa).<\/jats:p><\/jats:sec>Results<\/jats:title>Transcriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFN\u03b1 and not by IFN\u03b3 protein levels. IFN\u03b1 protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5\u2010year follow\u2010up. Genetic analysis revealed a significant association between IFN\u03b1 protein levels, a major histocompatibility (MHC) class II haplotype, and anti\u2010SSA antibody. Additional cellular analysis revealed that an MHC class II HLA\u2013DQ locus acts through up\u2010regulation of HLA class II molecules on conventional dendritic cells.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>We identified the predominance of IFN\u03b1 as a driver of primary SS variability, with IFN\u03b1 demonstrating an association with HLA gene polymorphisms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42265","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T22:49:34Z","timestamp":1655765374000},"page":"1991-2002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Variability of Primary Sj\u00f6gren's Syndrome Is Driven by Interferon\u2010\u03b1 and Interferon\u2010\u03b1 Blood Levels Are Associated With the Class II HLA\u2013DQ Locus"],"prefix":"10.1002","volume":"74","author":[{"given":"Diana","family":"Trutschel","sequence":"first","affiliation":[{"name":"Computational 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W.","family":"Thorball","sequence":"additional","affiliation":[{"name":"School of Life Sciences, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne, and Precision Medicine Unit Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Jonsson","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Haukeland University Hospital, and Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Lessard","sequence":"additional","affiliation":[{"name":"Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, and Department of Pathology University of Oklahoma Health Sciences Center Oklahoma City 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