{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T16:48:27Z","timestamp":1776876507735,"version":"3.51.2"},"reference-count":78,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"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 Evidence Based Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically identify immune cell phenotypes causally associated with oral lichen planus (OLP) susceptibility using Mendelian randomization (MR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This two\u2010sample MR study evaluated causal relationships between 731 immune cell phenotypes and OLP risk. Single nucleotide polymorphisms (SNPs) were linkage disequilibrium\u2010clumped (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0&lt;\u00a00.001, 10,000\u00a0kb), filtered by\n                      <jats:italic>F<\/jats:italic>\n                      \u2010statistic (&gt;10), and harmonized across datasets (palindromic SNPs with intermediate allele frequencies removed). Inverse variance weighting was the primary method, complemented by MR\u2010Egger, weighted median, and mode\u2010based estimations. Heterogeneity (Cochran's\n                      <jats:italic>Q<\/jats:italic>\n                      ), horizontal pleiotropy (MR\u2010Egger intercept, MR pleiotropy residual sum, and outlier), and leave\u2010one\u2010out analyses were used for sensitivity checks. Associations passing multiple\u2010testing correction were interpreted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty\u2010eight immune phenotypes demonstrated significant causal associations: 19 protective and 9 risk\u2010increasing. Five of six regulatory T\u2010cell (Treg) phenotypes showed protective effects, with odds ratios (ORs) ranging from 0.916 to 0.958, and CD3 on CD4 Tregs showing the strongest effect (OR\u00a0=\u00a00.916). CD8\u2010bright leukocytes showed the strongest risk association (OR\u00a0=\u00a01.487). Eight B cell phenotypes conferred protection, particularly human leukocyte antigen DR (HLA DR) on B cells (OR\u00a0=\u00a00.889). Monocyte phenotypes exhibited divergent effects: Myeloid\u2010derived suppressor cells were protective (OR\u00a0=\u00a00.840), whereas HLA DR\u2010expressing monocytes increased risk (OR range: 1.276\u20131.281).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides genetic evidence that OLP pathogenesis involves immunoregulatory imbalance between protective regulatory mechanisms and pathogenic effector responses. Findings support precision therapeutic strategies targeting specific immune pathways and offer insights for other oral autoimmune diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jebm.70096","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T07:27:06Z","timestamp":1765870026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Causal Associations Between Immune Cell Phenotypes and Oral Lichen Planus: A Large\u2010Scale Mendelian Randomization Study"],"prefix":"10.1111","volume":"18","author":[{"given":"Zirui","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Center for Stomatology West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Center for Stomatology West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianshu","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Center for Stomatology West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyan","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Center for Stomatology West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lunwei","family":"Kang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Center for Stomatology West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyu","family":"Xie","sequence":"additional","affiliation":[{"name":"Innovation Institute for Integration of Medicine and Engineering West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Center for Stomatology West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"Tianfu Jiangxi Laboratory  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ga","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Center for Stomatology West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"},{"name":"Department of Stomatology Informatics West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12260"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2005.01142.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13323"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjoms.2007.07.199"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2009.03.004"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2019.07.012"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/154411130201300405"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2010.00946.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2016.12.029"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12185777"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1023213"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24033038"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12405"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1182732"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.83981"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-023-01793-7"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110175"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202X.2003.22108.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1305684"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42358-024-00354-2"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13040-024-00385-x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2106858119"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01038-5"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0684-4"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","unstructured":"B.Elsworth M.Lyon T.Alexander et\u00a0al. \u201cThe MRC IEU OpenGWAS Data Infrastructure \u201d preprint bioRxiv August 10 2020.","DOI":"10.1101\/2020.08.10.244293"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05473-8"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy262"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx102"},{"issue":"6","key":"e_1_2_8_37_1","first-page":"1961","article-title":"Assessing the Suitability of Summary Data for Two\u2010Sample Mendelian Randomization Analyses Using MR\u2010Egger Regression: The Role of the I2 Statistic","volume":"45","author":"Bowden J.","year":"2016","journal-title":"International Journal of Epidemiology"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000559"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0255-x"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy258"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy101"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"issue":"3","key":"e_1_2_8_44_1","first-page":"1205","article-title":"Frequently Increased but Functionally Impaired CD4+CD25+ Regulatory T Cells in Patients With Oral Lichen Planus","volume":"39","author":"Zhou L.","year":"2016","journal-title":"Inflammation"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70113-X"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(19)30018-9"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34162-3"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31130-9"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.03.019"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3432"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040391"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/immadv\/ltaf020"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13537"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1231-2"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1999.00618.x"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2506"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00608.x"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2015.1004983"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-006-0204-8"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1998.00617.x"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-012-8297-3"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0806510"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(93)70082-5"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.12948"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-0172(10)80012-5"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-015-0239-y"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.17898"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01808"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.01.031"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2017.03.012"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12885"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-023-03138-0"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2013.06.016"},{"issue":"9","key":"e_1_2_8_74_1","first-page":"e938","article-title":"Oral Lichen Planus and Its Relationship With Systemic Diseases. A Review of Evidence","volume":"10","author":"Cassol\u2010Spanemberg J.","year":"2018","journal-title":"Journal of Clinical and Experimental Dentistry"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyaa288"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17117-4"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.15555.1"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2024.156815"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15112930"}],"container-title":["Journal of Evidence-Based Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jebm.70096","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jebm.70096","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jebm.70096","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T11:41:29Z","timestamp":1769946089000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jebm.70096"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":78,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/jebm.70096"],"URL":"https:\/\/doi.org\/10.1111\/jebm.70096","archive":["Portico"],"relation":{},"ISSN":["1756-5383","1756-5391"],"issn-type":[{"value":"1756-5383","type":"print"},{"value":"1756-5391","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70096"}}