Chronic ulcerative stomatitis: Evidence of autoimmune pathogenesis

Objectives: Chronic ulcerative stomatitis is a condition characterized by chronic, painful oral ulcers, whose pathogenesis is unknown. Patients demonstrate specific IgG autoantibodies against ΔNp63α, an epithelial nuclear transcription factor. The aim of this study was to investigate the role of patient autoantibodies in the disease pathogenesis. Methods: Three-dimensional in vitro tissues consisting of a fully differentiated, multilayer epithelium that mimics its in vivo counterpart were incubated with serum from patients with chronic ulcerative stomatitis. Results: Our results show a subepithelial detachment of the epithelium at the basement membrane interface, mimicking the oral ulcerations that are seen clinically. Expression of basement membrane proteins Type IV collagen and laminin-5 was unaltered, whereas the expression of α6β4 integrins, hemidesmosome components that attach basal keratinocytes to the basement membrane, was reduced, as determined by immunohistochemistry. Conclusion: These results give evidence that patient autoantibodies are pathogenic; and support an autoimmune pathogenesis in chronic ulcerative stomatitis.