Potential Utility of Combined Salivary Calprotectin and Anti-Cyclic Citrullinated Peptide in Rheumatoid Arthritis Assessment

<b>Background/Objectives</b>: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint damage. Although serum biomarkers such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) are widely used, blood-based testing is invasive. Saliva has emerged as a noninvasive diagnostic medium with clinical potential. This study aimed to evaluate the potential utility of salivary calprotectin and anti-CCP antibodies for discriminating patients with RA from healthy controls. <b>Methods</b>: Saliva samples were collected from 58 RA patients and 50 healthy controls. Salivary calprotectin and anti-CCP antibody levels were quantified using enzyme-linked immunosorbent assay. The diagnostic performance was evaluated using receiver operating characteristic curve analysis and logistic regression models that incorporated both biomarkers and clinical variables. <b>Results</b>: Patients with RA exhibited significantly higher salivary calprotectin and anti-CCP levels than controls (both <i>p</i> < 0.001). Calprotectin showed high sensitivity (79.31%), whereas anti-CCP displayed high specificity (84.00%). Salivary calprotectin was associated with disease duration and joint damage, while anti-CCP correlated with the erythrocyte sedimentation rate, RF, and serum anti-CCP. A multivariate model combining salivary biomarkers with clinical factors indicated an excellent diagnostic discrimination. <b>Conclusions</b>: Salivary calprotectin and anti-CCP antibodies show potential as complementary noninvasive biomarkers for distinguishing patients with established RA from healthy controls. However, as saliva samples were not collected at the time of initial diagnosis, these findings primarily support disease discrimination rather than early detection. Further prospective studies involving newly diagnosed and at-risk populations are required to clarify their role in early diagnosis, monitoring, and clinical implementation.