{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T03:14:33Z","timestamp":1783307673811,"version":"3.54.6"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oral leukoplakia (OL) is the most common oral potentially malignant disorder, defined as a white patch or plaque not attributable to other causes. While OL carries an inherent risk of malignant transformation, the underlying immunological changes remain poorly characterized. This study aimed to profile a broad panel of cytokines in saliva and plasma of OL patients in comparison to healthy controls, in order to elucidate local and systemic immunoinflammatory alterations associated with OL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Thirty patients with clinically and histopathologically confirmed OL and 30 age\u2010 and gender\u2010matched healthy controls were enrolled. Detailed clinical examinations were performed, including lesion characterization and psychosocial assessments. Unstimulated whole saliva and peripheral blood samples were collected, and concentrations of 13 cytokines\/chemokines (IL\u20101\u03b2, IL\u20106, IL\u20108\/CXCL8, IL\u201010, IL\u201012p70, IL\u201017A, IL\u201018, IL\u201023, IL\u201033, TNF\u2010\u03b1, IFN\u2010\u03b3, IFN\u2010\u03b12, and MCP\u20101\/CCL2) were measured using a multiplex bead\u2010based immunoassay. Group comparisons were performed using appropriate statistical tests (\n                      <jats:italic>\u03c7<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \/Fisher's exact test for categorical variables and\n                      <jats:italic>t<\/jats:italic>\n                      \u2010test or Mann\u2013Whitney\n                      <jats:italic>U<\/jats:italic>\n                      test for continuous variables), with statistical significance set at\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OL patients (mean age 52.4\u2009\u00b1\u200910.7\u2009years) and controls (59.9\u2009\u00b1\u200912.8\u2009years) showed no significant differences in gender, socioeconomic status, or psychological scores. Salivary levels of IL\u20101\u03b2, TNF\u2010\u03b1, MCP\u20101, IL\u20108, and IL\u201018 were significantly lower in OL patients compared to controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01 for all), whereas other salivary cytokines (IFN\u2010\u03b12, IFN\u2010\u03b3, IL\u20106, IL\u201010, IL\u201012p70, IL\u201017A, IL\u201023, IL\u201033) showed no significant differences. In contrast, plasma levels of IFN\u2010\u03b12, IL\u20106, IL\u201012p70, IL\u201017A, IL\u201018, and IL\u201033 were significantly higher in OL patients than in controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), indicating systemic inflammation, while plasma IL\u20101\u03b2, IFN\u2010\u03b3, TNF\u2010\u03b1, MCP\u20101, IL\u20108, IL\u201010, and IL\u201023 did not differ. No significant differences in salivary cortisol, liver enzymes, or hepatitis viral markers were observed between groups. Across histopathological subgroups, cytokine concentrations did not significantly differ between lesions graded as hyperkeratosis, OIN1, OIN2, or OIN3, although a trend toward higher plasma IL\u20106, IL\u201017A, and IL\u201018 levels was observed in cases with higher OIN grades.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings shed light on the inflammatory profile of OL. The decrease in salivary IL\u20101\u03b2, IL\u20108, TNF\u2010\u03b1, and MCP\u20101 may indicate a more suppressed local immune response, whereas the higher plasma levels of IL\u20106, IL\u201017A, IL\u201018, and IL\u201033 tend to be seen in lesions showing greater degrees of dysplasia. In particular, patients with higher OIN grades often display this systemic inflammatory shift, which may signal an increased risk of progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jop.70131","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T03:09:01Z","timestamp":1773198541000},"page":"682-694","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunological Biomarkers in Oral Leukoplakia According to Oral Intraepithelial Neoplasia (\n                    <scp>OIN<\/scp>\n                    ) Classification: A Comparative Analysis of Salivary and Plasma Cytokines"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6931-0806","authenticated-orcid":false,"given":"Hakan","family":"Y\u00fclek","sequence":"first","affiliation":[{"name":"Private Dental Clinic  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7564-4757","authenticated-orcid":false,"given":"Gaye","family":"Keser","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Radiology Marmara University, Faculty of Dentistry  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-0523","authenticated-orcid":false,"given":"Ba\u015fak","family":"Aru","sequence":"additional","affiliation":[{"name":"Immunology Department Yeditepe University, Faculty of Medicine  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7426-5587","authenticated-orcid":false,"given":"Filiz","family":"Namdar Pekiner","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Radiology Marmara University, Faculty of Dentistry  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5775-491X","authenticated-orcid":false,"given":"G\u00fclderen","family":"Yan\u0131kkaya Demirel","sequence":"additional","affiliation":[{"name":"Immunology Department Yeditepe University, Faculty of Medicine  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"issue":"6","key":"e_1_2_9_2_1","first-page":"680","article-title":"Oral Potentially Malignant Disorders: A Comprehensive Review","volume":"129","author":"Warnakulasuriya S.","year":"2020","journal-title":"Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology"},{"key":"e_1_2_9_3_1","first-page":"81","article-title":"Oral Leukoplakia: Present Views on Diagnosis, Management and Malignant Transformation","volume":"6","author":"Waal I.","year":"2019","journal-title":"Current Oral Health Reports"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12903\u2010023\u201003342\u2010y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2018.06.006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14301"},{"key":"e_1_2_9_7_1","volume-title":"A\u011f\u0131z Hastal\u0131klar\u0131 Tan\u0131 Kriterleri, Ay\u0131r\u0131c\u0131 Tan\u0131 ve Tedavi Yakla\u015f\u0131mlar\u0131","author":"\u00d6zbayrak S.","year":"2003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cden.2017.08.001"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/froh.2024.1363052"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973-029X.190900"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12095"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14295"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13810"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12339"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.08.011"},{"key":"e_1_2_9_16_1","unstructured":"E. 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