{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T06:09:30Z","timestamp":1778479770424,"version":"3.51.4"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"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>Background<\/jats:title>\n                    <jats:p>Oral lichen planus (OLP) is a chronic immune-mediated mucosal disorder with a heterogeneous clinical course and potential for malignant transformation. While T-cell dysfunction is central to its pathogenesis, the role of humoral immune responses, particularly food-specific IgG-mediated reactions, remains underexplored. This study aimed to comprehensively evaluate the cellular and humoral immune profiles in OLP patients and investigate their association with clinical phenotypes and inflammatory biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this retrospective cross-sectional study, 696 OLP patients were enrolled. Peripheral lymphocyte subsets (CD3\n                      <jats:sup>+<\/jats:sup>\n                      , CD4\n                      <jats:sup>+<\/jats:sup>\n                      , CD8\n                      <jats:sup>+<\/jats:sup>\n                      , CD19\n                      <jats:sup>+<\/jats:sup>\n                      , NK cells) were quantified by flow cytometry. Serum levels of food-specific IgG antibodies against 14 common antigens and inflammatory mediators (CRP, IL-6, TNF-\u03b1, IFN-\u03b3, IL-17A) were measured by ELISA. Patients were stratified by age, gender, and clinical type (erosive vs. non-erosive). Statistical analyses included correlation tests, logistic regression, and subgroup profiling based on immune status and IgG positivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OLP patients exhibited significant suppression of total T, helper T, cytotoxic T, B, and NK cells compared to healthy references. Food-specific IgG antibodies were detected in 57.6% of patients, with eggs being the most prevalent trigger. Female patients showed higher IgG positivity and elevated IL-6\/IL-17A levels. Erosive OLP was independently associated with longer disease duration, lower CD3\n                      <jats:sup>+<\/jats:sup>\n                      \/CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell counts, and higher IL-6, TNF-\u03b1, and IL-17A. IgG positivity was predicted by female gender, low CD3\n                      <jats:sup>+<\/jats:sup>\n                      \/CD4\n                      <jats:sup>+<\/jats:sup>\n                      counts, high B\/NK cells, and elevated IL-6, IL-17A, and CRP. Subgroup analysis identified a high-risk phenotype (immune-suppressed + IgG-positive) with the most severe erosive disease, highest inflammation, and multiple-food reactivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest a distinct immune-dietary interplay in OLP, where T-cell deficiency and food-specific IgG responses are closely linked to systemic inflammation and erosive disease. This supports a \u201cTwo-Hit\u201d pathogenic model and highlights the potential for combined immunomodulatory and dietary interventions in high-risk patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1804758","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:29:57Z","timestamp":1778477397000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune dysfunction and food-specific IgG associated erosive oral lichen planus: a two-hit pathogenic model"],"prefix":"10.3389","volume":"17","author":[{"given":"Yanjie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qigen","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Head Neck, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1177\/00220345251385966","article-title":"Oral lichen planus and systemic diseases","volume":"105","author":"Warnakulasuriya","year":"2026","journal-title":"J Dent Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2025.106431","article-title":"Patterns of circulating autoantibodies against desmoglein-1 and desmoglein-3 in the progression of oral lichen planus: a scoping review","volume":"181","author":"Sarasati","year":"2026","journal-title":"Arch Oral Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27020914","article-title":"Different approaches to oral lichen planus treatment: a narrative review","volume":"27","author":"Du\u015b-Ilnicka","year":"2026","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.7554\/elife.83981","article-title":"CD8+ tissue-resident memory T cells induce oral lichen planus erosion via cytokine network","volume":"12","author":"Qing","year":"2023","journal-title":"Elife"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jds.2021.07.024","article-title":"Predisposition of hypersensitivity in patients with exfoliative cheilitis","volume":"17","author":"Cai","year":"2022","journal-title":"J Dent Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1650705","article-title":"Food-specific IgG antibodies and body mass index: multivariate analysis of clinical correlations in underweight populations","volume":"16","author":"Zeng","year":"2025","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.jds.2021.10.002","article-title":"Direct immunofluorescence and immune function in patients with oral lichen planus","volume":"17","author":"Mao","year":"2022","journal-title":"J Dent Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.70056","article-title":"The impact of food specific IgG antibodies on migraine and its comorbidities","volume":"12","author":"Zhao","year":"2024","journal-title":"Immun Inflammation Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1720389","article-title":"Food-specific IgG-based elimination diet decreased IL-6, TNF-\u03b1, and CGRP and improved symptoms in adults with migraine","volume":"12","author":"Zhao","year":"2025","journal-title":"Front Nutr"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1332317","article-title":"Inflammatory cytokines and oral lichen planus: a Mendelian randomization study","volume":"15","author":"Chen","year":"2024","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.5051\/jpis.2018.48.4.213","article-title":"Factors affecting treatment outcomes in patients with oral lichen planus lesions: a retrospective study of 113 cases","volume":"48","author":"Park","year":"2018","journal-title":"J Periodontal Implant Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.673708","article-title":"Partners in leaky gut syndrome: intestinal dysbiosis and autoimmunity","volume":"12","author":"Kinashi","year":"2021","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-023-03374-w","article-title":"Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review","volume":"19","author":"Di Vincenzo","year":"2024","journal-title":"Intern Emerg Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.20510.1","article-title":"All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases","volume":"9","author":"Fasano","year":"2020","journal-title":"F1000Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.946248","article-title":"Gut microbiota, leaky gut, and autoimmune diseases","volume":"13","author":"Christovich","year":"2022","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1177\/0145561319867668","article-title":"Food-specific IgE and IgG antibodies in patients with chronic rhinosinusitis with nasal polyps: a case-control study","volume":"100","author":"Veloso-Teles","year":"2021","journal-title":"Ear Nose Throat J"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/eos.70040","article-title":"Analysis of peripheral blood antigens and their clinical value in oral lichen planus","volume":"133","author":"Huang","year":"2025","journal-title":"Eur J Oral Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jds.2024.03.002","article-title":"Potential different immune phenotypes of macrophages in oral lichen planus by integrating immunofluorescence double staining and single-cell RNA sequencing","volume":"19","author":"Zhang","year":"2024","journal-title":"J Dent Sci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-022-00657-5","article-title":"Associations between food-specific IgG and health outcomes in an asymptomatic physical examination cohort","volume":"19","author":"Wu","year":"2022","journal-title":"Nutr Metab (Lond)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.603050","article-title":"IgE and IgG antibodies as regulators of mast cell and basophil functions in food allergy","volume":"11","author":"Kanagaratham","year":"2020","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.jaci.2017.03.045","article-title":"Allergen-specific IgG antibody signaling through Fc\u03b3RIIb promotes food tolerance","volume":"141","author":"Burton","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1186\/s12903-024-04621-y","article-title":"Increased pathogenicity and pro-inflammatory capabilities of mucosal-associated invariant T cells involved in oral lichen planus","volume":"24","author":"Chen","year":"2024","journal-title":"BMC Oral Health"},{"key":"B23","article-title":"The role of food-specific IgG antibody test in diagnosis and treatment of mild recurrent aphthous ulcer","volume":"26","author":"Du","year":"2017","journal-title":"Shanghai Kou Qiang Yi Xue"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.5144\/0256-4947.2016.386","article-title":"Prevalence of IgG-mediated food intolerance among patients with allergic symptoms","volume":"36","author":"Shakoor","year":"2016","journal-title":"Ann Saudi Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14014","article-title":"A proof of concept pilot trial of probiotics in symptomatic oral lichen planus (CABRIO)","volume":"28","author":"Marlina","year":"2022","journal-title":"Oral Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.93788","article-title":"The IgG paradox in lipedema: more food sensitivities, less antibody production","volume":"17","author":"Amato","year":"2025","journal-title":"Cureus"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1804758\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:29:58Z","timestamp":1778477398000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1804758\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":26,"alternative-id":["10.3389\/fimmu.2026.1804758"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1804758","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]},"article-number":"1804758"}}