Dysregulation of micro-RNAs involved in TLR pathway in peripheral blood mononuclear cells and synovial fluid mononuclear cells of patients with enthesitis related arthritis form of juvenile idiopathic arthritis (HUM3P.254)

Abstract

Abstract Toll like receptor (TLR) pathway plays a major role in inflammatory arthritis. MicroRNA (miR)-146a, miR-155, miR-21 regulate downstream molecules of TLR signaling like IRAK-1 and TRAF-6. TLR pathway genes are generally upregulated in ERA-JIA. We studied expression of miR-146a, miR-155, miR-21, miR-210 and miR-26a in PBMC and SFMC of patients with ERA. RNA was isolated from PBMC (n=21) & SFMC (n=11) of ERA patients and PBMC of controls (n=11). The miRNA and target gene expressions were analysed by TaqMan qRT-PCR assays. Among 21 patients, 20 were boys. Mean disease onset age was 10.3Y & disease duration was 6Y. All had arthritis, 14 had enthesitis, 4 had uveitis, 7 had IBP and 2 had family history of HLAB27 related disease. No expression difference was seen in miR-146a, miR-155, miR-210 and miR-26a in PBMC of patients and controls but miR-21 was increased in patients. To check inflammatory site specific expression, comparison of SFMC and PBMC was done showing downregulation of miR146a and upregulation of miR-155, miR-21 and miR-210 in SFMC. Expression of miR-26a did not show any change. MiR-146a target genes i.e. IRAK-1 and TRAF-6 were upregulated in SFMC compared to PBMC. There is dysregulation of miRNAs regulating TLR pathway in mononuclear cells of patients with ERA-JIA especially at the chronic inflammation site. Down regulation of miR-146a, a key regulator may lead to over-expression of TLR downstream molecules like IRAK-1 and TRAF-6 thus perpetuating inflammation in ERA.