Tehran University of Medical Sciences Immunology and Genetics Journal 2645-4831 7 4 2024 12 22 268 273 Behnam Khazaei Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran Razieh Akhtar Student Research Committee, Zahedan University of Medical Sciences, Zahedan, Iran Hossein Ali Khazaei Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran Masoomeh Shirzaiy Oral and Maxillofacial Medicine, Oral and Dental Disease Research Center, Zahedan University of Medical Science, Zahedan, Iran Amin khazaei Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran Hossein Ansari Department of Epidemiology and Biostatistics, Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran 2025 01 23 2025 02 16 Background Recurrent Aphthous Stomatitis (RAS) is a common and painful condition characterized by recurrent ulcers in the oral mucosa, affecting a significant portion of the population and leading to considerable discomfort and decreased quality of life. Despite its prevalence, the underlying etiology of RAS remains poorly understood, with factors such as genetics, immune dysregulation, and environmental triggers being implicated. C-reactive protein (CRP) is an acute-phase protein primarily produced by the liver in response to inflammation, and its levels in serum can serve as a biomarker for systemic inflammatory conditions. This study aims to investigate the relationship between serum CRP levels and the occurrence of RAS seeking to elucidate the role of systemic inflammation in this condition. Methods In a cross-sectional study design, we enrolled 26 participants diagnosed with RAS according to established diagnostic criteria, alongside a control group of 26 healthy individuals matched for age and gender. Serum CRP levels were quantified using enzyme-linked immunosorbent assay (ELISA) methods, and demographic, clinical, and lifestyle data were collected through structured questionnaires. We employed statistical analyses, including t-tests and regression models, to assess the association between serum CRP levels and the frequency and duration of RAS. Results Our findings reveal significantly elevated serum CRP levels in individuals with RAS compared to healthy controls (p<0.04), indicating a potential link between systemic inflammation and the pathophysiology of RAS. Additionally, elevated CRP levels were associated with increased ulcer severity and prolonged healing time. Multivariate analyses further demonstrated that serum CRP could serve as an independent predictor of RAS severity, highlighting its potential role as a biomarker for disease activity. Conclusion In conclusion, our investigation provides compelling evidence that systemic inflammation, as indicated by elevated serum CRP levels, is associated with RAS. https://igj.tums.ac.ir/index.php/igj/article/view/170 https://igj.tums.ac.ir/index.php/igj/article/download/170/162