{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:57:43Z","timestamp":1773820663025,"version":"3.50.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to identify interferon (IFN)-related key genes in patients with Sj\u00f6gren\u2019s Disease (SjD) and to elucidate their specific associations with the heterogeneous clinical phenotypes and laboratory parameters of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bioinformatics analyses, including differentially expressed gene (DEG) screening, weighted gene co-expression network analysis (WGCNA), and machine learning, were conducted on dataset GSE84844 to identify IFN-related key genes. Based on the EULAR Sj\u00f6gren\u2019s syndrome disease activity index (ESSDAI), SjD patients with low, moderate, and high disease activity were enrolled, with 20 in each subgroup. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on peripheral blood mononuclear cells (PBMCs) from the 60 SjD patients and 15 healthy controls (HCs). Expression levels were compared between SjD patients and HCs, across disease activity subgroups, and correlated with clinical phenotypes and laboratory indicators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DEGs in SjD were significantly enriched in IFN-related signaling pathways. Five IFN-related hub genes were identified: CXCL10, DDX60L, IFIH1, JAK2, and NMI. qRT-PCR validation confirmed that all five genes were significantly upregulated in SjD patients compared to HCs (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). However, their expression did not significantly differ among SjD subgroups with varying levels of overall disease activity (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05). Importantly, these genes were differentially expressed in distinct clinical manifestations. For instance, elevated CXCL10 expression was observed in patients with interstitial lung disease (ILD), leukopenia, and anemia; JAK2 expression differed in rheumatoid arthritis comorbidity; IFIH1 expression also showed differences in those with Raynaud\u2019s phenomenon and ILD. Furthermore, certain genes were highly expressed in specific laboratory abnormalities: elevated erythrocyte sedimentation rate with CXCL10 and JAK2; hyperglobulinemia with CXCL10, DDX60L, IFIH1, and JAK2; and elevated immunoglobulin G with CXCL10, DDX60L, and IFIH1 (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies five IFN-related key genes (CXCL10, DDX60L, IFIH1, JAK2, and NMI) that are upregulated in SjD. Their expression patterns are not generalized markers of disease activity but are specifically linked to distinct clinical phenotypes and serological abnormalities. These findings provide novel mechanistic insights into the clinical heterogeneity of SjD and highlight CXCL10, JAK2, and IFIH1 as potential biomarkers for specific disease complications and promising candidates for targeted therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1762625","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:57:30Z","timestamp":1773817050000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering the interferon gene signature spectrum: association with the clinical heterogeneity of Sj\u00f6gren\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Ziyue","family":"Luo","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, 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