F. Abji1, R. Pollock2, K. Liang3, V. Chandran4, D. Gladman5
The IL-23/IL-17 axis is central to the pathogenesis of psoriatic arthritis (PsA). We aimed to identify Th17 signalling genes that are dysregulated in synovial fluid of PsA compared to osteoarthritis (OA) patients and to determine if differences in peripheral blood can distinguish PsA from psoriasis patients and controls.
Synovial fluid cells (SFCs) from 14 PsA and 9 OA patients were obtained and stored in TRIzol reagent. RNA was isolated by phenol-chloroform extraction and purified with RNeasy miniprep kits. Total RNA was extracted from PAXgene whole blood from 20 PsA, 20 psoriasis without arthritis (PsC) and 11 controls. Quantitative RT-PCR arrays were used to profile expression of 84 genes related to the Th17 regulatory network. Fold change differences were compared by Mann-Whitney U-test with false discovery rate (FDR) correction (FDR<0.05).
In PsA compared to OA SFCs, a total of 33 genes were up-regulated and 27 genes were down-regulated. Signalling molecules (such as STAT3, FOXP3) were highly expressed in PsA SFCs, while cytokines (such as IL17F, IL6) were more predominant in OA SFCs after non-supervised hierarchal clustering. Nine genes (MMP3, CCL1, IL17C, CCL20, IL17F, IL3, CXCL5, IL6 and CX3CL1) had concordant expression in SFCs and in peripheral blood cells (PBCs) of PsA compared to PsC and/or controls.
We identified expression differences in Th17 signalling genes in PsA compared to OA SFCs, with an elevation of signalling molecules and attenuation of cytokine expression in PsA. A subset of genes was concordant in PBCs; these may thus be potential biomarkers of PsA.
PMID: 29148410 [PubMed]
Received: 15/03/2017 - Accepted : 01/08/2017 - In Press: 09/11/2017