{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:43:26Z","timestamp":1782924206153,"version":"3.54.5"},"reference-count":17,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Sj\u00f6gren disease (SjD) is a heterogeneous autoimmune disease. We aimed to investigate blood transcriptomic signatures and disease progression among three recently defined clusters of patients with SjD: (1) B cell active disease with low symptom burden (BALS), (2) high systemic activity (HSA), and (3) low systemic activity with high symptom burden (LSAHS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed transcriptomic data from the ASSESS cohort (GSE140161; n\u00a0=\u00a0351). Patients were classified into the three clusters previously described. Within BALS, an evolutive subgroup was defined based on need for new immunosuppressants and\/or occurrence of lymphoma (BALS subgroup of patients with progressive\/evolving disease [BALS_Evol]). Differential expression analysis and Gene Set Enrichment Analysis were performed to evaluate subgroup\u2010specific signatures and biologic pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both BALS and HSA displayed robust types I\/II interferon (IFN)\u2010stimulated gene up\u2010regulation compared to LSAHS. BALS exhibited stronger IFN activity and inflammatory signaling than HSA, particularly in the evolutive subgroup (BALS_Evol). This subgroup showed enrichment of IFN\u03b1\/\u03b3, tumor necrosis factor \u03b1, interleukin\u20106, complement activation, and mechanistic target of rapamycin (mTOR) complex 1 pathways, indicating a hyperinflammatory and dysregulated immune state linked to disease progression. In contrast, compared with BALS, the HSA cluster displayed attenuated IFN and KRAS pathway activity, coupled with activation of MYC, mTOR, and oxidative phosphorylation, suggesting a molecular shift toward proliferation and metabolism that may promote systemic disease evolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IFN signaling is a hallmark of both HSA and BALS clusters. In BALS, it may drive early disease progression, which can be replaced later by proliferative pathways leading to an HSA. These findings pave the way for new hypotheses regarding the mechanisms driving disease progression in SjD.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70251-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70251","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:12:10Z","timestamp":1781161930000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Molecular Pathways Supporting Sj\u00f6gren Disease Clusters and Disease Progression"],"prefix":"10.1002","author":[{"given":"Sacha E.","family":"Silva\u2010Saffar","sequence":"first","affiliation":[{"name":"GenHotel \u2010 European Research Laboratory for Rheumatoid Arthritis Universit\u00e9 \u00c9vry Paris\u2010Saclay  Evry\u2010Courcourconnes France"},{"name":"Paris\u2010Saclay University, Inserm, Commissariat \u00e0 l'Energie Atomique Immune diseases, microbiology and innovative therapies (IDMIT\/UMRS1184)  Fontenay\u2010aux\u2010Roses &amp; Le Kremlin\u2010Bic\u00eatre France"},{"name":"Department of Immuno\u2010Rheumatology H\u00f4pital Bic\u00eatre, Universit\u00e9 Paris\u2010Saclay, Assistance Publique \u2013 H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0866-3824","authenticated-orcid":false,"given":"Yann","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Centre for Research in Epidemiology and Statistics Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 Sorbonne Paris Nord, Inserm, Institut national de recherche pour l'agriculture, l'alimentation et l'environnement  Paris France"},{"name":"Department of Internal Medicine H\u00f4pital Beaujon, Universit\u00e9 Paris Cit\u00e9, Assistance Publique \u2013 H\u00f4pitaux de Paris  Clichy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00e8le","family":"Seror","sequence":"additional","affiliation":[{"name":"Paris\u2010Saclay University, Inserm, Commissariat \u00e0 l'Energie Atomique Immune diseases, microbiology and innovative therapies (IDMIT\/UMRS1184)  Fontenay\u2010aux\u2010Roses &amp; Le Kremlin\u2010Bic\u00eatre France"},{"name":"Department of Immuno\u2010Rheumatology H\u00f4pital Bic\u00eatre, Universit\u00e9 Paris\u2010Saclay, Assistance Publique \u2013 H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9469-946X","authenticated-orcid":false,"given":"Jacques\u2010Eric","family":"Gottenberg","sequence":"additional","affiliation":[{"name":"Service de Rhumatologie H\u00f4pitaux Universitaires de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Niarakis","sequence":"additional","affiliation":[{"name":"Molecular, Cellular and Developmental Biology Unit, Centre de Biologie Integrative University of Toulouse, Paris Saclay University, Centre national de la recherche scientifique  Toulouse France"},{"name":"Lifeware Group Inria Saclay\u2010\u00eele de France  Palaiseau France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Mariette","sequence":"additional","affiliation":[{"name":"Paris\u2010Saclay University, Inserm, Commissariat \u00e0 l'Energie Atomique Immune diseases, microbiology and innovative therapies (IDMIT\/UMRS1184)  Fontenay\u2010aux\u2010Roses &amp; Le Kremlin\u2010Bic\u00eatre France"},{"name":"Department of Immuno\u2010Rheumatology H\u00f4pital Bic\u00eatre, Universit\u00e9 Paris\u2010Saclay, Assistance Publique \u2013 H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-0733","authenticated-orcid":false,"given":"Gaetane","family":"Nocturne","sequence":"additional","affiliation":[{"name":"Paris\u2010Saclay University, Inserm, Commissariat \u00e0 l'Energie Atomique Immune diseases, microbiology and innovative therapies (IDMIT\/UMRS1184)  Fontenay\u2010aux\u2010Roses &amp; Le Kremlin\u2010Bic\u00eatre France"},{"name":"Department of Immuno\u2010Rheumatology H\u00f4pital Bic\u00eatre, Universit\u00e9 Paris\u2010Saclay, Assistance Publique \u2013 H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1702514"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23472-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42238"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-03051-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(19)30042-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224503"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00340-5"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.43096"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42265"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key360"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103064"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102704"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ard.2025.07.021"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217646"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2018-000701"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead096"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1156774"}],"container-title":["Arthritis &amp; 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