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 One hundred and twenty Egyptian patients with RA and 130 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 = 0.85, 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. In RA group, 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 as a predictor of RA risk and APRIL as an excellent biomarker of disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.

Comprehensive overview of microRNA function in rheumatoid arthritis

“… 233 In addition, patients with established rather than early RA exhibited higher expression of serum miR-223 than unaffected controls. 234 , 235 A study by Ouboussad et al suggested a pronounced increase in the expression levels of serum miR-22 after progression from the preclinical state to early RA. Serum miR-22 is therefore deemed an important predictor of the onset and development of RA.…”

“… 235 , 244 Taha et al later proposed the conflicting view that serum miR-155 expression does not differ between RA patients and controls. 234 Overall, the intrinsic and extrinsic factors affecting circulating miRNA levels have not been fully characterized. The sex, age, race, and lifestyle of the subjects, techniques employed for miRNA analysis, study design and stage of disease may all contribute to the differences in circulating miRNA signatures.…”

miR-223: An Effective Regulator of Immune Cell Differentiation and Inflammation

“…Rheumatoid arthritis (RA) is a chronic inflammatory disease. Studies have demonstrated that miR-223 is significantly higher in the plasma, serum and peripheral mononuclear cells (PBMCs) of RA patients than those of controls, indicating that miR-223 could be associated with the development, progression and severity of RA 92 , 93 . The reliability of the biological functions of miR-223 in RA has been confirmed by accurately measuring the AUC value, and sensitivity and specificity of miR-223 94 .…”

Application of NGS Technology in Understanding the Pathology of Autoimmune Diseases

“…Moreover, expression profile of miRNAs is variable and depends on diseases entities [ 106 ]. In the case of RA many studies revealed correlation between different clinical parameters and dysregulation of expression analyzed miRNAs [ 41 , 107 , 108 ]. Many studies show that level of microRNA may help to predict therapeutic effects [ 70 , 109 , 110 , 111 , 112 ].…”