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The systemic immune-inflammation biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), have been proposed as indicators of the inflammatory burden, but data in SjD remain limited. This retrospective multicenter Italian study aimed to evaluate the NLR, PLR, and SII in exocrine SjD patients and across specific EGM. Consecutive patients fulfilling the 2016 ACR\/EULAR classification criteria for SjD and with available full blood count data were included. Patients were classified as having exocrine or extraglandular SjD according to the presence of specific EGM. The NLR, PLR, and SII were calculated and compared across disease phenotypes and activity levels. Among 239 SjD patients (96% female, median age 59\u00a0years), 70% presented at least one EGM. Extraglandular SjD patients had longer disease duration (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04) and higher frequencies of hypergammaglobulinemia (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.05), anti-nuclear antibodies (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0003), anti-SSA antibodies (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04), and rheumatoid factor (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04). Overall, the median NLR, PLR, and SII did not differ between exocrine and extraglandular SjD. However, patients with arthritis showed higher NLR (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02), PLR (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), and SII (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005), while patients with interstitial lung disease displayed higher SII (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01). Extraglandular SjD patients with moderate-to-high disease activity showed increased NLR and SII (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.004, for both). Systemic immune-inflammation biomarkers are inexpensive, readily available and easy to calculate. The NLR, PLR, and SII are associated with specific inflammatory phenotypes and higher disease activity in Italian SjD patients. Prospective studies are warranted to confirm these preliminary findings.\n                  <\/jats:p>","DOI":"10.1007\/s11739-026-04394-y","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:03:42Z","timestamp":1779451422000},"page":"2109-2119","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The systemic immune-inflammation biomarkers in Sj\u00f6gren\u2019s disease: associations with disease activity and extraglandular manifestations in a multicentric Italian cohort"],"prefix":"10.1007","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5207-7913","authenticated-orcid":false,"given":"Stefano","family":"Stano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-5930","authenticated-orcid":false,"given":"Venerito","family":"Vincenzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Giannotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Cacciapaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Catamer\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4963-0663","authenticated-orcid":false,"given":"Maria","family":"Iacovantuono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7905-8413","authenticated-orcid":false,"given":"Paola","family":"Conigliaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Monosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Domanico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Urgesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Vitale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-1729","authenticated-orcid":false,"given":"Maria Sole","family":"Chimenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0474-5344","authenticated-orcid":false,"given":"Florenzo","family":"Iannone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4524-9566","authenticated-orcid":false,"given":"Giuseppe","family":"Lopalco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"issue":"12","key":"4394_CR1","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.55563\/clinexprheumatol\/i8iszc","volume":"42","author":"C Baldini","year":"2024","unstructured":"Baldini C, Chatzis LG, Fulvio G, La Rocca G, Pontarini E, Bombardieri M (2024) Pathogenesis of Sj\u00f6gren\u2019s disease: one\u00a0year in review 2024. 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