Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Gene Expression Profiling Reveals Dysregulation of Innate Immune Genes in Synovial Fluid Mononuclear Cells of Patients with Enthesitis Related Arthritis.
Aggarwal1, Amita, Myles2, Arpita, Tuteja3, Amit
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Lucknow, India
Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India
The center for Genomic applications, New Delhi, India
Enthesitis related arthritis (ERA) category of juvenile idiopathic arthritis (JIA) is said to arise in genetically predisposed individuals in response to environmental triggers. Gene expression profiling has helped identify new pathogenic pathways in other JIA categories and have opened new avenues for therapy like IL-1Ra in Systemic JIA. Data on ERA is limited thus we studied expression profile of ERA patients' peripheral blood and synovial fluid mononuclear cells (PBMCs and SFMCs). PBMCs from polyarticular JIA (polyJIA) patients and healthy subjects were used as controls.
RNA from PBMCs of ERA, polyJIA patients and healthy controls (n=17, 8, 8) and 7 ERA SFMCs were converted to labelled cRNA and hybridised to Illumina Human WG-6_v3_BeadChip chips. Expression profiles were analysed using Genespring software. Genes differentially expressed at a fold-change cut-off of >= 2.0 and detection p values of < 0.05 were subjected to hierarchical clustering and pathway analysis. Selected genes of interest were validated at RNA and protein level.
Although ERA PB could be distinguished from ERA SF, control PB and polyJIA PB using supervised clustering, yet, there was no statistically significant difference in PBMC gene expression of ERA, polyJIA and control groups. However, there was significant difference between gene expression profile of SFMCs and PBMCs of patients with ERA, with 131 genes being overexpressed and 216 being under-expressed in SFMCs. 182 genes were involved in 13 pathways, none of which was significantly dysregulated as per gene ontology analysis. Amongst these, highest number of genes (36) had an immunological function. Out of these CD1b, CD1d, MHC class II alpha and beta chain, soluble CD163, chemokines CXCR3 and CXCL16 were over expressed whereas genes related to NK cell function, namely, Granzyme H, KLRF1, KIR3DL3, NKG7 and other genes like CD244, CD248, FAIM3 were under-expressed.
ERA SFMC has 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 under-expressed. All these genes have been associated with pathology of several inflammatory diseases, including rheumatoid arthritis and other JIA categories. Therefore, we hypothesise that they may contribute to disease exacerbation in ERA.
To cite this abstract, please use the following information:
Aggarwal, Amita, Myles, Arpita, Tuteja, Amit; Gene Expression Profiling Reveals Dysregulation of Innate Immune Genes in Synovial Fluid Mononuclear Cells of Patients with Enthesitis Related Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :294