Oral lichen planus (OLP) is a chronic inflammatory mucosal disorder characterized by immune dysregulation and an elevated risk of malignant transformation into oral squamous cell carcinoma (OSCC) (Kumari et al., 2022). Clinically, OLP presents with diverse manifestations, ranging from asymptomatic reticular lesions to painful erosive and ulcerative forms (González-Moles and Ramos-García, 2024, González-Moles et al., 2021), often leading to significant impairment in patients’ quality of life (Manchanda et al., 2024). Painful erosions and ulcers in OLP may resemble those of other autoimmune mucocutaneous disorders, further complicating differential diagnosis (Elenbaas et al., 2022).

Accurate diagnosis of OLP remains challenging due to overlapping clinical and histopathological features with other mucosal conditions, including lichenoid drug reactions (Ismail et al., 2007), mucous membrane pemphigoid (Douley & Fricain, 2023), pemphigus vulgaris (De et al., 2020), oral lupus erythematosus, and graft-versus-host disease (Binnie et al., 2024) Although clinical indicators such as Wickham’s striae may aid in diagnosis (Gururaj et al., 2021), the heterogeneity of OLP presentation necessitates more reliable biomarkers for improved classification and management (Binnie et al., 2024).

OLP is commonly classified into reticular, erosive, and ulcerative subtypes based on clinical appearance. Traditionally considered as distinct clinical forms, recent evidence suggests that these subtypes may reflect a continuum of disease severity rather than separate entities. The shared pathogenesis involves T cell–mediated immune responses that induce basal keratinocyte apoptosis and epithelial atrophy (Nukaly et al., 2024). Variations in lesion type may therefore represent differences in immune activity intensity, chronicity, or tissue response. Notably, corticosteroid therapy has been shown to modulate disease severity, with some patients exhibiting progression to more severe forms while others improve to milder types, underscoring the dynamic nature of the disease (Chinani-Wu et al., 2001).

Although the precise etiology of OLP remains unclear, immune dysregulation plays a central role in driving transitions between subtypes (Manchanda et al., 2024). Despite histopathological similarities among clinical forms (Rotaru et al., 2020), there is a pressing need for novel biomarkers that reflect epithelial integrity and desmosomal stability in the context of chronic inflammation. Such markers could support accurate diagnosis, risk stratification, and monitoring of disease progression.

Desmogleins, the primary components of desmosomes, are crucial for maintaining cell–cell adhesion in stratified squamous epithelium. Desmoglein 1 (Dsg-1) is predominantly expressed in the suprabasal layers (stratum spinosum and granulosum), contributing to the cohesion of differentiated epithelial layers. In contrast, desmoglein 3 (Dsg-3) is mainly localized to the basal and lower suprabasal layers, such as the stratum basale and stratum spinosum, where it plays a key role in anchoring basal keratinocytes to the basement membrane (Didona & Hertl, 2022). These proteins are integral to the structural and functional integrity of the oral mucosa (Thomas et al., 2020).

Alterations in desmosomal proteins have been implicated in autoimmune blistering diseases, such as pemphigus vulgaris (PV), where anti-Dsg autoantibodies directly impair epithelial cohesion (Amagai & Stanley, 2012). While OLP is primarily driven by T cell–mediated mechanisms, the detection of serum autoantibodies against Dsg-1 and Dsg-3 has emerged as a potential adjunct marker, especially in erosive or ulcerative presentations that mimic PV.

Several studies have identified IgG autoantibodies against Dsg-3 in OLP patients, particularly those with mucosal involvement (Schmidt et al., 2018). Although the significance of these circulating autoantibodies remains poorly understood, they may offer both diagnostic and mechanistic insights (Rambhia et al., 2018). For instance, anti-Dsg-1 levels have been reported to be lower in reticular-type OLP compared to healthy controls (Lukač et al., 2006). In contrast, erosive-type OLP has been associated with increased anti-Dsg-3 levels (Muramatsu et al., 2016, Vahide et al., 2017) and decreased anti-Dsg-1 levels (Gholizadeh et al., 2015, Lukač et al., 2006). Ulcerative-type OLP, however, tends to test negative for both autoantibodies despite severe epithelial breakdown (Raha et al., 2023).

These findings suggest that desmoglein autoantibodies may arise as a secondary phenomenon following epithelial damage, where desmosomal degradation exposes antigens and triggers humoral immune responses (Patsatsi et al., 2014, Weiss et al., 2015). Alternatively, these autoantibodies could actively contribute to disease pathogenesis by weakening epithelial cohesion. Nevertheless, no definitive causal relationship has been established.

Different patterns of anti-Dsg-1 and anti-Dsg-3 autoantibody expression across OLP subtypes may be associated with disease progression, supporting the hypothesis that ulcerative-type OLP could evolve from reticular-type via an erosive intermediate. The clinical detection of these antibodies may assist in disease subtyping, prediction of progression, and therapeutic decision-making, particularly in atypical or severe cases where diagnosis is uncertain. Furthermore, their presence may reflect a mixed immune response involving both cellular and humoral pathways, offering a more comprehensive understanding of OLP pathogenesis.

This scoping review aims to investigate the circulating patterns of anti-Dsg-1 and anti-Dsg-3 autoantibodies in reticular, erosive, and ulcerative forms of OLP, to elucidate their roles in epithelial integrity and disease progression. Understanding the significance of desmoglein autoantibodies in OLP may reveal new diagnostic markers and therapeutic targets for this chronic mucosal disease.