{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:31:28Z","timestamp":1792096288906,"version":"4.4.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"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>Assessing labial salivary gland exocrinopathy is a cornerstone in primary Sj\u00f6gren\u2019s syndrome. Currently this relies on the histopathologic diagnosis of focal lymphocytic sialadenitis and computing a focus score by counting lym=phocyte foci. However, those lesions represent advanced stages of primary Sj\u00f6gren\u2019s syndrome, although earlier recognition of primary Sj\u00f6gren\u2019s syndrome and its effective treatment could prevent irreversible damage to labial salivary gland. This study aimed at finding early biomarkers of primary Sj\u00f6gren\u2019s syndrome in labial salivary gland combining metabolomics and machine-learning approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used a standardized targeted metabolomic approach involving high performance liquid chromatography coupled with mass spectrometry among newly diagnosed primary Sj\u00f6gren\u2019s syndrome (n=40) and non- primary Sj\u00f6gren\u2019s syndrome sicca (n=40) participants in a prospective cohort. A metabolic signature predictive of primary Sj\u00f6gren\u2019s syndrome status was explored using linear (logistic regression with elastic-net regularization) and non-linear (random forests) machine learning architectures, after splitting the data set into training, validation, and test sets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 126 metabolites accurately measured, we identified a discriminant signature composed of six metabolites with robust performances (ROC-AUC = 0.86) for predicting primary Sj\u00f6gren\u2019s syndrome status. This signature included the well-known immune-metabolite kynurenine and five phospholipids (LysoPC C28:0; PCaa C26:0; PCaaC30:2; PCae C30:1, and PCaeC30:2). It was split into two main components: the first including the phospholipids was related to the intensity of lymphocytic infiltrates in salivary glands, while the second represented by kynurenine was independently associated with the presence of anti-SSA antibodies in participant serum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results reveal an immuno-lipidomic signature in labial salivary gland that accurately distinguishes early primary Sj\u00f6gren\u2019s syndrome from other causes of sicca symptoms.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1205616","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T23:07:56Z","timestamp":1689376076000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["An immuno-lipidomic signature revealed by metabolomic and machine-learning approaches in labial salivary gland to diagnose primary Sj\u00f6gren\u2019s syndrome"],"prefix":"10.3389","volume":"14","author":[{"given":"Geoffrey","family":"Urbanski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris","family":"Chabrun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Delattre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Lacout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Blanchet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Chao de la 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