THU0048 Stat3-Regulated Gene Expression in Circulating CD4+ T Cells Discriminates RA Patients Independently of Clinical Parameters in Early Arthritis: A Validation Study

BackgroundRheumatoid arthritis is a T cell mediated disease of immune dysregulation whose pathogenesis remains incompletely understood. We previously identified a 12-gene “signature”, enriched for STAT3 target genes, which was predictive of rheumatoid arthritis (RA) in circulating CD4+ T cells of early arthritis patients1. Subsequent investigations have confirmed the importance of IL-6 mediated STAT3 signalling in circulating CD4+ T cells as an early event in RA pathogenesis2.ObjectivesTo carry out an independent replication study, seeking to validate our previous findings with respect to a 12-gene expression signature in CD4+ T cells of early arthritis patients, interpreting the findings in the context of other clinically relevant baseline parameters.MethodsGene expression in highly purified peripheral blood CD4+ T cells from disease modifying anti-rheumatic drug (DMARD)- and steroid-naïve patients with suspected inflammatory arthritis was measured using Illumina microarray technology. A nested analysis focussed on normalised expression of those transcripts hybridised by the 12 probes identified during the previous study. Concurrent STAT3 pathway activation was determined in CD4+ T cells by paired whole blood flow cytometry, and detailed clinical and serological data were recorded for all participants. Analyses included the use of univariate tests, hierarchical clustering and logistic regression.ResultsIn this independent cohort of 161 early arthritis patients, normalised expression of ten out of the 12 CD4+ T cell “signature” genes studied differed significantly between patients presenting with RA and alternative diagnoses (p1.3-fold difference; p