Background/Purpose:  Enthesitis related arthritis (ERA) is the most common category of JIA in Asia. Identifying dysregulated microRNA may help in understanding the pathogenesis of ERA. Thus we compared miRNA profile in PBMC from ERA subjects and healthy controls (HC) and further compared between PBMC with SFMC to understand the changes at the site of inflammation

Methods:  MiRNA profile was determined using Agilent Human miRNA Microarray chips using PBMC from HC and ERA, and SFMC from ERA (n=8 each). The dysregulated miRNA were validated by qRT-PCR in 25 patients and 11 healthy controls. In silico target prediction and pathway analysis was also done for these miRNAs.

Results: Eight miRNAs were differentially expressed in the PBMC from ERA patients relative to HC (p<0.25). Moreover, 90 miRNA were dysregulated (38 higher and 52 lower; p<0.05) in SFMC compared to PBMC from ERA Patients qRT-PCR validated upregulation of miR-21, miR-126, miR-130a and downregulation of miR-150 ( p<0.05) in ERA-PBMC (n=25) relative to HC-PBMC (n=11). In addition, expression of miR-155, miR-21, miR-34a, miR-210, miR-29b was upregulated and miR-146a, miR-150, miR-126, miR-130a and miR-26a was downregulated (p<0.05) in paired SFMCs relative to PBMC (n=9). Among the 4 dysregulated miRNAs in ERA-PBMC, relative to HC-PBMC, only miR-21 and miR-150 showed a positive association with their levels in SFMC (p<0.05). PDCD4, predicted target of miR-21 and miR-150, was up-regulated in SFMCs compared to ERA-PBMCs. In silico analysis revealed that the targets of differentially expressed miRNAs belong immune signaling pathways like MAPK signaling pathways, TLR signaling pathways, T cell receptor signaling pathways, mTOR signaling pathways, Wnt signaling pathways.

Conclusion:  Differential expression of miR-21 and miR-150 in ERA may regulate T cell activation via PDCD4. Predicted target genes for other dysregulated miRNA found at the site of inflammation suggest a role of multiple immune pathways in ERA pathogenesis.