Elevated Nesfatin-1 Level in Synovium and Synovial Fluid is Associated with Pro-Inflammatory Cytokines in Patients with Rheumatoid Arthritis

Shuo Zhang,1 Genxiang Rong,2 Yayun Xu,3 Juehua Jing1 1Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Juehua JingDepartment of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui, 230032, People’s Republic of ChinaEmail jjhhu@sina.comBackground: Adipocytokines have been proven to be involved in the progression of autoimmune diseases, including rheumatoid arthritis (RA). Nesfatin-1, a newly discovered adipokine, has recently been reported to possess potent anti-inflammatory, antiapoptotic, and antioxidative properties. However, its role in RA has not yet been reported. Therefore, this study aimed to determine nesfatin-1 levels in the synovium and synovial fluid (SF) of patients with RA and examine their correlation with clinical manifestations and proinflammatory cytokine levels.Methods: Synovium and SF samples were collected from patients with RA and non-RA patients during joint surgery. Immunohistochemistry was used to measure nesfatin-1 protein expression in the synovium. Enzyme-linked immunosorbent assay was used to measure nesfatin-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Pearson correlation analysis was used to evaluate the correlations between nesfatin-1 levels, RA clinical features, and proinflammatory cytokines. The diagnostic value of synovium nesfatin-1 for RA was assessed using receiver operating characteristic (ROC) curve analysis.Results: The results showed that nesfatin-1, IL-1β, and TNF-α levels in the synovium were significantly higher in patients with RA than in controls, with age and body mass index as covariates. Moreover, the results of Pearson correlation analysis showed that nesfatin-1 levels were positively correlated with IL-1β and TNF-α levels in the synovium of patients with RA. Furthermore, there was a positive relationship between synovium nesfatin-1 levels and rheumatoid factor in patients with RA. Additionally, the results of the ROC curve analysis revealed an area under the curve of 0.733 with 77.5% sensitivity and 60.0% specificity for synovium nesfatin-1 in discriminating patients with RA from controls.Conclusion: These findings suggest that increased nesfatin-1 levels in the synovium may be associated with proinflammatory cytokines and RA severity.Keywords: rheumatoid arthritis, adipocytokine, nesfatin-1, synovium, synovial fluid, pro-inflammatory cytokines