Evaluation of serum midkine levels in patients with Recurrent Aphthous Stomatitis

Recurrent Aphthous Stomatitis (RAS) is a common, painful, and relapsing inflammatory disease characterized by oral ulcerations that affects a significant portion of the population. Although its etiopathogenesis has not yet been fully elucidated, it is thought to be associated with multiple factors including genetic predisposition, microbial agents, hematologic deficiencies, psychological stress, and immune system dysregulation. The complexity of these interactions underscores the need for reliable biomarkers in the diagnostic and therapeutic processes. Midkine, a heparin-binding growth factor expressed in various tissues, plays a role in several pathophysiological processes, particularly inflammation. It has been shown that midkine levels are elevated in many diseases associated with Th1 type immune responses. However, no studies have been identified in the literature that investigate serum midkine levels in patients with RAS. This study aims to evaluate the potential role of midkine in the pathogenesis of RAS and to explore its association with disease activity. A total of 44 patients diagnosed with RAS and 44 age and sex matched healthy volunteers were included in the study. Detailed clinical histories were obtained from all participants, and laboratory parameters including hs-CRP, vitamin B12, folate, hemoglobin, iron, and ferritin were measured. Serum midkine levels were assessed using the ELISA method. Statistical analyses were performed using SPSS version 30.0 and Minitab 18 software. Our findings demonstrated that serum midkine levels were significantly higher in the patient group compared to the control group (p = 0.006). ROC analysis revealed that a cut-off value of 0.228 ng/mL for midkine yielded a specificity of 97.7% and a sensitivity of 22.7%, suggesting that midkine may serve as a highly specific supportive biomarker in the diagnosis of RAS. No statistically significant correlation was found between serum midkine levels and disease activity or severity. Additionally, serum hemoglobin and vitamin B12 levels were significantly higher in the control group compared to the patient group. In conclusion, this study suggests that midkine may be considered a potential biomarker in the diagnostic evaluation and elucidation of the pathogenesis of RAS. These findings provide a scientific basis for future research investigating the relationship between midkine and RAS. Further large-scale studies at both serum and tissue levels are warranted to clarify the role of midkine in the pathophysiology of RAS.