{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:04:13Z","timestamp":1780985053874,"version":"3.54.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"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>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The diagnosis of Sj\u00f6gren\u2019s Disease (SjD) remains challenging due to the non-specific nature of sicca symptoms and the need for invasive biopsies. This pilot study aimed to investigate the potential of salivary Substance P (SP), a neuropeptide involved in glandular regulation and neurogenic inflammation, as a novel, non-invasive biomarker to differentiate patients with SjD from those with non-autoimmune Non-Sj\u00f6gren sicca syndrome (NSS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Unstimulated whole saliva samples were collected from three groups of female participants: 13 patients classified as SjD according to ACR\/EULAR criteria, 13 patients with idiopathic NSS symptoms who did not meet the criteria, and 13 healthy controls (CTRL). Salivary SP concentrations were measured using a specific enzyme-linked immunosorbent assay (ELISA). Clinical, serological, and histopathological data were recorded for correlation analyses. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of salivary SP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Salivary SP levels were significantly higher in SjD patients (mean 92.2 \u00b1 15.503 pg\/ml) compared to both NSS patients (30.39 \u00b1 4.08 pg\/ml, p &amp;lt; 0.005) and healthy controls (39.93 \u00b1 5.97 pg\/ml, p &amp;lt; 0.005). No significant difference was found between the NSS and CTRL groups. ROC analysis demonstrated that salivary SP could distinguish SjD from NSS, with an area under the curve (AUC) of 0.8225 (p = 0.005). At a cut-off value of 47.63 pg\/ml, sensitivity was 77% and specificity was 85%. A positive association was observed between salivary SP levels and the presence of ANA autoantibodies in the SjD cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Salivary SP appears to be elevated in patients with SjD compared to those with NSS in this preliminary study, suggesting a potential diagnostic signal that warrants further investigation. Although the observed differences hint at possible utility as a non-invasive biomarker related to neuroimmune dysregulation, the diagnostic accuracy observed should be interpreted with caution due to the limited sample size and the exploratory nature of the findings. Larger, prospective, and well-powered studies are needed to confirm these preliminary observations, to assess the robustness of salivary SP as a diagnostic tool, and to determine its potential clinical applicability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1851367","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:44:37Z","timestamp":1780983877000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Substance P as a potential salivary biomarker to differentiate Sj\u00f6gren\u2019s disease from non-Sj\u00f6gren sicca syndrome: a pilot study"],"prefix":"10.3389","volume":"17","author":[{"given":"Pamela","family":"Rosso","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, National Research Council (CNR)","place":["Rome, Italy"]},{"name":"Ma.CRO Lifescience Srl","place":["Roma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Fico","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, National Research Council (CNR)","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Di Criscio","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, National Research Council (CNR)","place":["Rome, Italy"]},{"name":"Department of Sense Organs, Sapienza University of Rome","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Priori","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Complessa Rheumatology, Department of Internal Medicine and Medical Specialties, Azienda Ospedaliero-Universitaria (AOU) Policlinico Umberto I","place":["Rome, 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