Association of circulating micro-RNAs (miR-21-5p and miR-142-3p (and tumor necrosis factor-α with Rheumatoid Arthritis

Abstract

Micro-RNAs (miRNAs) become a promising biomarker for diagnosis due to their stability and reproducibility and could be help to find a new effective treatment. This study is designed to evaluate the diagnostic utility and clinical significance of circulating micro-RNAs (miR-21-5p and miR-142-3p (and tumor necrosis factor-α (TNF-α) for patient with RA and to assess their correlation with disease activity. This case control study involved sixty patients and 30 apparently healthy subjects as control group. The diagnosis was done depending on the classification criteria of American college of rheumatology-European league against rheumatism (ACR- EULAR). Expression levels of circulating miRNA were determined by two step reversed transcription polymerase chain reactions (RT- PCR). The concentrations of TNF-α, anti-citrullinated protein antibodies(ACPA) and C- reactive protein(CRP) were estimated by Enzyme linked immune-sorbent assay technique ( ELISA ). The expression level of circulating miRNA- 21- 5p and miRNA - 142- 3p was significantly elevated (P <0.01) in patients group as well as the levels of blood ESR, serum CRP, ACPA, and TNF-α compared to controls. There are significant differences (P < 0.01) in miRNA- 21- 5p levels between different patients groups, while the expression of miR-142-3p show non-significant difference (p>0.05). It is found that miRNA- 21-5p expression levels are significantly correlated with RA activity. Both miR-21-5p and miR-142-3p have significant positive correlation with levels of CRP, ACPA, and TNF-α. The level of TNF-α have significant positive correlation with both of CRP and ACPA also with the DAS-28 and CDAI. In conclusion, circulating miR-21- 5p and miRNA - 142- 3p may be associated to RA pathogenesis due to their positive correlation with inflammatory cytokine TNF-α, CRP and ACPA, therefore these miRNAs might be considered new targets for RA treatment, and alterations in their expression could be used for diagnosis and monitoring the disease activity and treatment response.