Synovial fluid mononuclear cell gene expression profiling suggests dysregulation of innate immune genes in enthesitis-related arthritis patients

Abstract

Objective. Microarray studies have provided insight into the pathogenesis of systemic JIA and have opened new avenues for therapy. Data on the pathogenesis of the enthesitis-related arthritis (ERA) category of JIA are limited, thus we studied the expression profile of ERA patients' peripheral blood and SF mononuclear cells (PBMCs and SFMCs, respectively). PBMCs from healthy subjects were used as controls. Methods. RNA from PBMCs of ERA patients (n = 17) and healthy controls (n = 8) and seven ERA SFMCs were converted to labelled cRNA and hybridized to Illumina Human WG-6_v3_BeadChip chips. Expression profiles were analysed using GeneSpring software. Selected genes of interest were validated by real-time PCR. Results. There was no significant difference in PBMC gene expression of ERA and control groups. However, there was a significant difference between expression profiles of SFMCs and PBMCs of patients with ERA, with 131 genes being overexpressed and 216 being underexpressed in SFMCs. Among genes involved with immune function, cluster of differentiation (CD)1b, CD1d, MHC class II alpha and beta chain, and soluble CD163 were overexpressed, whereas genes related to NK cell function, namely, Granzyme H, killer cell lectin-like receptor subfamily F member 1, killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail (KIR3DL3), natural killer group 7 (NKG7) and other genes like CD244, CD248 and Fas apoptotic inhibitory molecule 3 (FAIM3) were underexpressed. Conclusion. ERA SFMCs had a distinct gene expression profile from PBMCs and had higher expression of genes associated with antigen presentation, scavenger function, chemotaxis and proteases, whereas genes involved in NK cell function, cell adhesion and inhibitors of apoptosis were underexpressed.