Immune dysfunction and food-specific IgG associated erosive oral lichen planus: a two-hit pathogenic model

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.

In this retrospective cross-sectional study, 696 OLP patients were enrolled. Peripheral lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺, CD19⁺, 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-α, IFN-γ, 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.

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⁺/CD4⁺ T-cell counts, and higher IL-6, TNF-α, and IL-17A. IgG positivity was predicted by female gender, low CD3⁺/CD4⁺ 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.

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 "Two-Hit" pathogenic model and highlights the potential for combined immunomodulatory and dietary interventions in high-risk patients.