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The aim of this study was to determine serum protein biomarkers for lymphoma development and to advance our understanding of the functional mechanisms underlying lymphomagenesis in SjD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with SjD and incident, current lymphoma (n=18) with serum sampled before treatment and at 6, 12 and 24 months of follow-up, and four patients sampled 1\u20135 years before lymphoma diagnosis (pre-lymphoma) were included. SjD without lymphoma (n=21), SjD with historical lymphoma (n=6) and healthy blood donors (n=39) served as controls. Differentially expressed proteins between groups were analysed using the Olink Target 96 Immuno-Oncology panel applying a false discovery rate (FDR) adjusted p value of 0.05. Protein-derived interferon activation scores (pIFN scores) were calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We determined 18 differentially expressed proteins in SjD with incident lymphoma compared with both SjD without lymphoma and healthy controls. Among the top upregulated proteins were TNFSF14, FGF2, IL8, CD40 and CXCL13, where CXCL13 was the only protein with decreased levels at follow-up. We also observed upregulated expression of CD40 in the SjD pre-lymphoma group compared with SjD without lymphoma and healthy controls. All SjD patient groups presented elevated pIFN scores compared with healthy controls, where SjD sampled pre-lymphoma showed the most distinct IFN activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified altered protein expression and an increased IFN system activation in SjD with incident lymphoma and pre-lymphoma. This knowledge may contribute to earlier detection of high-risk patients, identification of therapeutic targets and may ultimately improve SjD patient outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005897","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:15:14Z","timestamp":1761214514000},"page":"e005897","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted proteomics identifies differentially expressed proteins in Sj\u00f6gren\u2019s disease with incident lymphoma"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7230-8990","authenticated-orcid":false,"given":"Juliana","family":"Imgenberg-Kreuz","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Section of Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, 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