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While previous genome\u2010wide association studies (GWAS) and transcriptomic analyses have identified genes associated with SjS, predictive models based on single\u2010cell resolution are limited. In this study, single\u2010cell RNA sequencing (scRNA\u2010seq) data from peripheral blood mononuclear cells (PBMCs) of SjS patients were analyzed to map immune cell alterations linked to the disease. Compared with healthy controls, SjS patients displayed decreased proportions of na\u00efve\n                    <jats:italic>CD8<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    T cells and\n                    <jats:italic>Helios FOXP3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>lo<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>CD4<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    Tregs, alongside increased frequencies of\n                    <jats:italic>CTLA<\/jats:italic>\n                    \u22124\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>CD8<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    inhibitory T cells and\n                    <jats:italic>TRDC<\/jats:italic>\n                    \u03b3\u03b4 T cells. Using machine learning, a predictive model for SjS diagnosis was developed based on a 12\u2010gene signature (SjS. Sig:\n                    <jats:italic>GIMAP7<\/jats:italic>\n                    ,\n                    <jats:italic>PSMB8<\/jats:italic>\n                    ,\n                    <jats:italic>CD27<\/jats:italic>\n                    ,\n                    <jats:italic>CCR7<\/jats:italic>\n                    ,\n                    <jats:italic>TAGAP<\/jats:italic>\n                    ,\n                    <jats:italic>UQCR10<\/jats:italic>\n                    ,\n                    <jats:italic>HCLS1<\/jats:italic>\n                    ,\n                    <jats:italic>LCK<\/jats:italic>\n                    ,\n                    <jats:italic>TNFAIP3<\/jats:italic>\n                    ,\n                    <jats:italic>ISG15<\/jats:italic>\n                    ,\n                    <jats:italic>GIMAP4<\/jats:italic>\n                    , and\n                    <jats:italic>HLA<\/jats:italic>\n                    \u2010\n                    <jats:italic>DRB1<\/jats:italic>\n                    ), which effectively differentiated patients from healthy individuals. Key genes such as\n                    <jats:italic>CD27<\/jats:italic>\n                    ,\n                    <jats:italic>PSMB8<\/jats:italic>\n                    ,\n                    <jats:italic>HCLS1<\/jats:italic>\n                    ,\n                    <jats:italic>LCK<\/jats:italic>\n                    ,\n                    <jats:italic>UQCR10<\/jats:italic>\n                    , and\n                    <jats:italic>GIMAP4<\/jats:italic>\n                    were validated in clinical samples through flow cytometry and real\u2010time quantitative PCR. These findings provide insights into the immune landscape of SjS at a single\u2010cell resolution and propose a reliable molecular signature for diagnosis and immune monitoring.\n                  <\/jats:p>","DOI":"10.1002\/imo2.70106","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T13:36:07Z","timestamp":1779975367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene expression signatures from single\u2010cell transcriptomics predict Sj\u00f6gren's syndrome"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2533-4769","authenticated-orcid":false,"given":"Shumin","family":"Cheng","sequence":"first","affiliation":[{"name":"The Seventh Affiliated Hospital Sun Yat\u2010sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yan","sequence":"additional","affiliation":[{"name":"The Seventh 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