Abstract
Recurrent aphthous ulceration (RAU) is a prevalent inflammatory condition affecting the oral mucosa. However, the localized epithelial junctional changes and their connection to immune cell distribution are not well understood. This study sought to characterize junction-associated protein expression and compartment-specific lymphocyte distribution in RAU. This retrospective, multicenter, paired tissue study included 56 consecutive patients with clinically and histopathologically confirmed RAU. Semiquantitative immunohistochemistry was employed to compare E-cadherin, claudin-1, and claudin-6 expression. Comparisons were made between ulcer-adjacent non-ulcerated regenerative epithelium and morphologically preserved distant mucosa from the same patient. The study also evaluated cluster of differentiation 4 (CD4)-, cluster of differentiation 8 (CD8)-, and cluster of differentiation 20 (CD20)-positive lymphocytes in both intraepithelial and subepithelial/ulcer-base compartments. All distant mucosal samples exhibited strong expression of the three junctional proteins. In contrast, within the ulcer-adjacent epithelium, E-cadherin expression was weak in 35.7% and moderate in 64.3% of cases. Claudin-1 was absent in 17.9% and weak in 82.1%, while claudin-6 was absent in 71.4% and weak in 28.6%. Each marker demonstrated significantly lower expression in all paired cases (p < 0.001). Descriptively, CD8-positive lymphocytes were consistently present intraepithelially in all cases, whereas CD20-positive lymphocytes were absent. The ulcer base and adjacent subepithelial tissue contained CD4-, CD8-, and CD20-positive lymphocytes in all cases. RAU is consistently linked to a localized reduction of epithelial junctional proteins and distinct compartmental lymphocyte patterns. These findings suggest epithelial junctional remodeling within the RAU microenvironment, though they do not confirm functional barrier impairment or causality.