Evaluation of Desmoglein-3 Autoantibodies in the Tissues of Oral Lichen Planus and Correlation with Disease Severity

Oral lichen planus (OLP), a chronic disease and one of the most common dermatoses of the oral mucosa, is characterized by white streaks in a lacelike pattern on the tongue and/or buccal mucosa. The disease is also accompanied by chronic inflammation, the degree of which, correlates with the intensity of the symptoms.

OLP occurs more frequently than the cutaneous form and tends to be more persistent and more resistant to treatment. It affects one to two percent of the general adult population, with a higher prevalence in the female gender, and occurs predominantly in adults over 40, although younger adults and children may be affected .

The most common site of oral involvement is the buccal mucosa followed by the tongue and gingiva, but any site of the oral mucosa can be affected. Clinically, OLP is classified as reticular, atrophic, erosive, plaque-type, and bullous. The reticular pattern is the most common form. It is generally asymptomatic and requires no treatment. In contrast, atrophic-erosive forms usually manifest as erythematous, ulcerative lesions associated with symptoms, fluctuating from mild burning sensation to severe pain, interfering with eating and speaking .

Furthermore, OLP is considered a potentially malignant disorder with a transformation rate of about 1.09%, with greater risk among those with atrophic-erosive forms.

The etiology and pathogenesis of OLP are not completely understood. Several factors have been implicated in the etiology and several hypotheses have been proposed for its pathogenesis.

It is believed that OLP represents an abnormal immune reaction in which keratinocytes are recognized as an antigen, secondary to changes in the antigenicity of the cell surface. This elicits an immune response characterized by invasion of inflammatory cells into the subepithelial layer of connective tissue with degeneration of the epithelium of the basement membrane However, the antigen or antigens triggering factors have not been identified.

Many controversies exist about the pathogenesis of OLP. A large body of evidence supports the role of immune dysregulation in the pathogenesis. The various mechanisms hypothesized to be involved in immunopathogenesis include humoral immunity, antigen-specific cell-mediated immune response, non-specific mechanisms, and autoimmune response.

Humoral immunity has been reported to play a role in the pathogenesis of OLP in addition to the presence of immunoglobulins, fibrinogen, and C3 complement in the basement membrane at the lesional and perilesional tissue Furthermore, concentrations of salivary IgG and IgA subclasses may be changed .

Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes, followed by antigen-specific keratinocyte killing by CD8+ cytotoxic T-cells.

Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis .

The possibility of the presence of circulating antibodies was previously indicated against desmoglein 3 (Dsg3) in patients with OLP.

Desmogleins (Dsgs) are the main components of cellular coherence in the epidermis and mucosal surfaces. They are consisting of (Dsg1), (Dsg2), (Dsg3), and (Dsg4). Dsg3 antigen is expressed in the basement membrane zone of the epidermis keeping the cells from detachment.

Dsgs are the victims of autoantibody reaction in some autoimmune bullous diseases such as pemphigus vulgaris and bullous pemphigoid causing disruption of desmosomes and consequent acantholysis.

In 2006, Lukac et al. demonstrated significantly higher concentrations of circulating autoantibodies against Dsg3 among erosive OLP patients and in patients with reticular OLP .

In a recent study including 100 OLP patients, 65% of the patients showed the presence of at least one type of autoantibodies in their serum. Dsg3 autoantibody was positive in 16% of the patients .

Furthermore, Saad et al, in 2018, showed increased levels of Dsg3 autoantibodies in the serum of patients with erosive OLP at baseline and after the use of topical Tacrolimus 0.1%. The results revealed a statistically significant decrease in the level of Dsg3 autoantibodies during the follow-up period.

In 2022, El-Rifaie et al detected that the level of Dsg3 autoantibodies in the serum of OLP patients was significantly higher as compared to normal control persons.

However, it is difficult to infer whether the anti-Dsg3 autoantibodies in lichen planus are of primary pathogenic significance or are a result of epitope spreading which is known to occur in autoimmune diseases. These autoantibodies may be increased as an etiologic agent in OLP or due to inflammatory damage to basal keratinocytes. This damage releases the Dsg3 proteins which act as auto-antigens for autoantibodies formation in the circulatory blood .

All the studies were concerned with detecting Dsg3 autoantibodies level in the serum of OLP patients. Unfortunately, such results do not prove the source of Dsg3 autoantibodies to be the OLP lesions. Thus, the present study will be carried out to detect the level of Dsg3 autoantibodies in tissues affected by atrophic/bullous erosive OLP trying to elucidate the actual role of Dsg3 autoantibodies in the etiopathogenesis of OLP.