Serum A Proliferation-Inducing Ligand and MicroRNA-223 are Associated with Rheumatoid Arthritis: Diagnostic and Prognostic Implications

Abstract Background: Current blood-based tests for rheumatoid arthritis (RA) have inherent limitations, necessitating the need for additional new biomarkers for its diagnosis and monitoring disease activity and responsiveness to therapy. microRNAs (miRNAs) and a proliferation-inducing ligand (APRIL) are deregulated in RA and were linked to its pathogenesis. This study investigated serum levels of APRIL, miR-223 and miR-155 in RA patients, their potential as diagnostic and prognostic biomarkers, and their correlation with disease activity and clinicopathological data. Methods: 120 Egyptian patients with RA and 30 healthy controls were included. Serum miRNAs and APRIL were assayed by RT-qPCR and ELISA, respectively. Results: Serum APRIL and miR-223 were significantly upregulated, while miR-155 was unchanged in RA patients compared to controls. Serum miR-223 discriminated RA patients from controls with AUC=0.83, whereas serum APRIL superiorly distinguished the two groups with AUC=1 (sensitivity and specificity= 100% at cutoff>4.19 ng/ml) by receiver-operating-characteristic analysis. Serum miR-223 was a significant predictor for RA diagnosis in multivariate logistic regression analysis. Serum APRIL was positively correlated with disease activity score (DAS28-CRP). Serum miR-223 expression was positively correlated with serum miR-155, APRIL levels and with the presence of subcutaneous nodules. Serum miR-155 levels were correlated with antinuclear antibody titer in reverse direction. Conclusion: our results suggest serum APRIL and miR-223 could serve as potential biomarkers of RA, with miR-223 is a predictor of RA risk and APRIL is an excellent biomarker for disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.