Serum Claudin-1 and Sestrin-2 Levels in Recurrent Aphthous Stomatitis: A Case-Control Study

Introduction: Recurrent aphthous stomatitis is a chronic inflammatory condition characterized by recurrent painful oral mucosal ulcers. Epithelial barrier-related alterations and oxidative stress have been proposed to be associated with its pathophysiology. Objectives: This study aimed to evaluate serum Claudin-1 and Sestrin-2 levels in patients with recurrent aphthous stomatitis and to assess their associations with clinical disease activity. Methods: This study was designed as an observational cross-sectional case-control study. Forty patients with active recurrent aphthous stomatitis and forty age- and sex-matched healthy volunteers were included in the study. Serum Claudin-1 and Sestrin-2 levels were measured using an enzyme-linked immunosorbent assay. Intergroup comparisons, correlations, and receiver operating characteristics were performed. Results: Serum Claudin-1 levels were significantly lower in the patient group (p=0.005). Serum Sestrin-2 levels, however, did not differ statistically between the patient and control groups. Claudin-1 levels showed a moderate negative correlation with monthly ulcer attack frequency (rho =−0.32, p=0.044). In addition, serum Claudin-1 levels showed a strong positive correlation with serum Sestrin-2 levels (rho=0.74, p<0.001). Conclusions: Lower serum Claudin-1 levels and their inverse correlation with monthly ulcer frequency suggest an association between serum Claudin-1 and ulcer attack frequency in RAS. However, because of the observational cross-sectional design, it cannot be determined whether reduced Claudin-1 contributes to RAS development, results from active ulceration, or reflects concurrent inflammatory activity at the time of sampling. Because Claudin-1 and Sestrin-2 were measured only in serum, these findings do not demonstrate oral mucosal tight-junction disruption or epithelial barrier dysfunction. Given the small sample size, serum-only biomarker assessment, and only modest discriminatory performance in ROC analysis, the results should be interpreted as preliminary and hypothesis-generating rather than diagnostically applicable.