Serum miRNA-186-3P and miRNA-382-3P constitute a novel Diagnostic miRNA signature for palindromic rheumatism

Background: Palindromic rheumatism (PR) is a unique disease characterized by the intermittent inflammation of different joints that may progress to a variety of immune-related diseases. Unclear diagnostic criteria have limited the research on its pathogenesis and treatment options. Recently, microRNAs (miRNAs) have been used in the diagnosis of various diseases; however, the role of miRNAs in PR diagnosis remains unexplored. Using next-generation high-throughput sequencing (NGS), this study aimed to screen miRNAs specifically expressed in the serum of patients with PR to construct a diagnostic signature and verify its diagnostic efficacy. Methods: Patients with PR (N=4), patients with rheumatoid arthritis (RA; N=3), and healthy controls (N=3) were included in an exploration cohort. Differentially expressed miRNAs were screened using NGS to construct diagnostic signatures and bioinformatics tools were used to perform target gene enrichment analysis of the top 25 differentially expressed miRNAs, both upregulated and downregulated. RT-qPCR was used to verify the differential expression of the diagnostic signatures in the three validation cohorts of patients with PR (N=27) and RA (N=30), and healthy controls (N=31), and the diagnostic efficiency of the diagnostic signatures was evaluated using receiver operator characteristic (ROC) curves. Results: A total of 130 differentially expressed miRNAs–35 upregulated and 95 downregulated miRNAs–were found in the PR exploration cohort, which differed between both RA and healthy controls. miRNA-186-3p showed the largest upregulated difference, and miRNA-382-3p showed the largest downregulated difference, and consequently, were selected to construct the diagnostic signature. In the ROC analysis of the validation cohort, the diagnostic signature produced an area under the ROC curve (AUC) of 1 (95% CI 1.000-1.000) compared with healthy controls. For patients with RA, the diagnostic signature produced an AUC of 0.915 (95% CI 0.842-0.988). However, miRNA-186-3p and miRNA-382-3p levels were not associated with disease activity in patients with PR. Conclusion: A diagnostic signature comprising miRNA-186-3p and miRNA-382-3p can effectively diagnose and differentiate PR from RA. This study provides a basis for the creation of a clinical miRNA signature for the diagnosis of PR. Overall design: This study aimed to screen differentially expressed miRNAs in PR samples and compare them to those in RA and healthy control samples using next-generation high-throughput RNA sequencing to construct miRNA signatures for PR diagnosis and verify their diagnostic efficacy. Additionally, bioinformatics tools were used to perform target gene enrichment analysis on differentially expressed miRNAs, offering new insights into defining PR diagnostic criteria and studying its pathogenesis.