{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:20:49Z","timestamp":1787678449163,"version":"build-2784847793"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Patients with primary Sj\u00f6gren disease (pSD) are prone to develop non\u2010Hodgkin lymphoma (NHL), but relevant biomarkers are lacking. We aimed to determine new biomarkers predictive of NHL in patients with pSD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two hundred six patients with pSD fulfilling American College of Rheumatology\/EULAR 2016 criteria were included and divided into three groups: pSD, lymphoproliferative pSD (Arl\u2010pSD), and NHL\u2010pSD. Deep flow cytometry immunophenotyping of B and T cell compartments as well as serum interferon\u2010\u03b1 (IFN\u03b1) quantification were coupled to clinical, biologic, and histopathologic data analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified CD11c<jats:sup>+<\/jats:sup> FcRL5<jats:sup>+<\/jats:sup> tissue\u2010like memory B cells and IFN\u03b3<jats:sup>+<\/jats:sup> TNF\u03b1<jats:sup>+<\/jats:sup> conventional T cells as significantly associated with NHL in pSD. These clusters showed progressive enrichment in Arl\u2010pSD and NHL\u2010pSD as compared to pSD. The combination of these two population abundances discriminates patients with NHL\u2010pSD with a sensitivity of 78.9% and a specificity of 76.8%, thus overcoming alone the performance of the sum of conventional clinical and biologic markers such as cryoglobulinemia vasculitis, parotid enlargement, adapted clinical EULAR Sj\u00f6gren's Syndrome Disease Activity Index, rheumatoid factor antibodies, low C4 and elevated serum IFN\u03b1 levels (68.4% and 78.0%, respectively). CD11c<jats:sup>+<\/jats:sup> FcRL5<jats:sup>+<\/jats:sup> tissue\u2010like memory B cells were associated with occurrence of mucosa\u2010associated lymphoid tissue (MALT) marginal\u2010zone NHL, whereas IFN\u03b3<jats:sup>+<\/jats:sup> TNF\u03b1<jats:sup>+<\/jats:sup> conventional T cells were more indicative of non\u2010MALT B cell NHL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We unveil novel biomarkers of NHL in pSD based on an integrative analysis coupling deep immunophenotyping and clinical, biologic, and histopathologic data. Furthermore, these markers allow distinguishing B cell NHL subtypes in pSD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.43207","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T06:09:56Z","timestamp":1745820596000},"page":"1394-1406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Deep Immunophenotyping and Clustering Identifies Biomarkers Predictive of Lymphoma in Primary Sj\u00f6gren Disease"],"prefix":"10.1002","volume":"77","author":[{"given":"Cindy","family":"Marques","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology Groupe Hospitalier Piti\u00e9\u2010Salp\u00eatri\u00e8re, AP\u2010HP, Sorbonne Universit\u00e9 and Centre de R\u00e9f\u00e9rence des Maladies Auto\u2010Immunes Syst\u00e9miques Rares, Centre de R\u00e9f\u00e9rence des Maladies Auto\u2010Inflammatoires et de l'Amylose inflammatoire and Immunology\u2010Immunopathology\u2010Immunotherapy (i3), Sorbonne Universit\u00e9, INSERM UMR S 959  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9713-1132","authenticated-orcid":false,"given":"Paul","family":"R\u00e9gnier","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology Groupe Hospitalier Piti\u00e9\u2010Salp\u00eatri\u00e8re, AP\u2010HP, Sorbonne Universit\u00e9 and Centre de R\u00e9f\u00e9rence des Maladies Auto\u2010Immunes Syst\u00e9miques Rares, Centre de R\u00e9f\u00e9rence des Maladies Auto\u2010Inflammatoires et de l'Amylose inflammatoire and Immunology\u2010Immunopathology\u2010Immunotherapy (i3), Sorbonne Universit\u00e9, INSERM UMR S 959  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Maciejewski\u2010Duval","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology 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