{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:25:11Z","timestamp":1793125511390,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The diagnosis of Sj\u00f6gren\u2019s disease (SjD) in patients without autoantibodies against Ro\/SSA is a major challenge. We aimed to identify novel autoantibodies in SjD that may facilitate the diagnostic procedure for Ro\/SSA negative SjD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IgG and IgA autoantibody reactivity of 94 potential candidate autoantigens for SjD, selected from a discovery screen of 1,629 human antigens coupled to Luminex beads and prior knowledge about potential biological relevance, were examined in serum of SjD patients (n=347) using Luminex and ELISA technology. Healthy (HC, n=118) and non-Sj\u00f6gren\u2019s sicca syndrome (NSS, n=44) individuals served as controls. To assess disease specificity, the novel autoantibodies were also measured in serum of patients with Rheumatoid Arthritis (RA, n=50), Systemic Lupus Erythematosus (SLE, n=49), and Systemic Sclerosis (SSc, n=37). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>45 novel autoantibodies were significantly (p \u2264 0.05) more prevalent in SjD than in HC and were detected in up to 19% of the SjD cohort. The most common autoantibodies were against CCL4, M5, TMPO and OAS3. Some of the novel autoantibodies were associated with extraglandular disease manifestations, such as anti-TONSL or anti-IL6 with pulmonary involvement. We have developed a three and five marker panel for the detection of Ro\/SSA negative patients, consisting of anti-FNBP4, anti-SNRPC, anti-CCL4, anti-M3 and anti-KDM6B, which had a sensitivity of up to 46% with a specificity of 95% (SjD vs. HC). Both panels discriminate these patients from HC, whereas the three-marker more effectively differentiates between Ro\/SSA negative patients and NSS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Novel autoantibodies will facilitate the diagnosis of Ro\/SSA negative patients with SjD, in particular our predictive panel will be useful in the diagnosis and differentiation of these patients from healthy and NSS individuals in a clinical context. In addition, the autoantibodies may also be useful for risk stratification of extraglandular manifestations.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1524940","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T06:34:05Z","timestamp":1738564445000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification of novel autoantibodies in Sj\u00f6gren\u2019s disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Fiona","family":"Engelke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Budde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"De 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