{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:32:21Z","timestamp":1790677941320,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We undertook this study to analyze whole blood gene expression and to investigate the role of B cell genes in primary Sj\u00f6gren's syndrome\u2013related non\u2010Hodgkin lymphoma (primary SS\u2010NHL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral whole blood samples were collected from 345 well\u2010phenotyped patients with primary SS enrolled in the prospective Assessment of Systemic Signs and Evolution in Sj\u00f6gren's Syndrome (ASSESS) cohort. Transcriptomic analysis was performed using human Clariom S Arrays (Affymetrix). In our primary analysis, we considered patients with incident lymphoma (i\u2010primary SS\u2010NHL) as the case group and all patients without lymphoma as the comparison group. In our sensitivity analyses, we considered all patients with primary SS\u2010NHL, including those with a history of lymphoma (h\u2010primary SS\u2010NHL), as the case group and primary SS patients without lymphoma, stratified on their risk factors of lymphoma, as the comparison group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010one patients with primary SS\u2010NHL (including 8 with i\u2010primary SS\u2010NHL and 13 h\u2010primary SS\u2010NHL) were eligible for transcriptomic analysis; we compared these patients to 324 primary SS controls without lymphoma, including 110 with moderate to severe disease activity and 61 with no risk factor of lymphoma. Functional clustering analyses revealed an enrichment of genes related to innate and adaptive immunity, including B cell\u2013related genes. Bruton's tyrosine kinase (BTK) and a proliferation\u2010inducing ligand (APRIL) genes were overexpressed before the occurrence of lymphoma in patients with incident lymphoma compared with patients without lymphoma. In sensitivity analyses, BTK was consistently up\u2010regulated across all comparisons performed. BTK expression was associated with risk of lymphoma on multivariate analyses, which considered 9 validated predictors of lymphoma in primary SS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BTK and APRIL were overexpressed in the peripheral blood of primary SS patients prior to lymphoma. The association between BTK, APRIL, and primary SS\u2010NHL requires confirmation in other prospective cohorts.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42550-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42550","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T13:34:53Z","timestamp":1682688893000},"page":"1798-1811","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Association Between Bruton's Tyrosine Kinase Gene Overexpression and Risk of Lymphoma in Primary Sj\u00f6gren's Syndrome"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1070-8830","authenticated-orcid":false,"given":"Pierre\u2010Marie","family":"Duret","sequence":"first","affiliation":[{"name":"Department of Rheumatology Colmar Civilian Hospital  Colmar France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Schleiss","sequence":"additional","affiliation":[{"name":"CNRS, Immunopathologie et Chimie Th\u00e9rapeutique\/Laboratory of Excellence Medalis, Institut de Biologie Mol\u00e9culaire et Cellulaire  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lou","family":"Kawka","sequence":"additional","affiliation":[{"name":"National Reference Centre For Rare Systemic Autoimmune Diseases, Department of Rheumatology Strasbourg University Hospital, University of Strasbourg  Strasbourg 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