GENETIC AND MOLECULAR INSIGHTS INTO PEMPHIGUS VULGARIS WITH ORAL INVOLVEMENT: IMPLICATIONS FOR BIOLOGIC THERAPY

Abstract

Pemphigus vulgaris (PV) is a chronic autoimmune mucocutaneous disorder characterized by intraepithelial blistering and erosions, primarily affecting the oral mucosa. Oral manifestations often precede cutaneous lesions and are frequently the earliest clinical indicators of the disease. The pathogenesis of PV involves autoantibody-mediated disruption of desmosomal adhesion molecules, especially desmoglein-3 (DSG3) and desmoglein-1 (DSG1). However, genetic predisposition plays a critical role in determining disease susceptibility and expression. This review synthesizes the current knowledge on the genetic factors underlying pemphigus vulgaris with oral involvement (PV-OI), including human leukocyte antigen (HLA) associations, non-HLA immune-related genes, desmosomal gene polymorphisms, and recent findings from genome-wide association studies (GWAS). It also explores the implications of epigenetic regulation and gene-environment interactions in the context of PV-OI.