Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis
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Gene expression profiling may be used to stratify patients by disease severity to test the hypothesis that variable disease outcome has a genetic component. In order to define unique expression signatures in African American rheumatoid arthritis (RA) patients with severe erosive disease, we undertook a gene expression study using samples of RNA from peripheral blood mononuclear cells (PBMCs). RNA from baseline PBMC samples of 96 African American RA patients with early RA (<2 years disease duration) was hybridized to cDNA probes of the Illumina Human HT-V3 expression array. Expression analyses were performed using the ca. 25,000 cDNA probes, and then expression levels were compared to the total number of erosions in radiographs of the hands and feet at baseline and 36 months. Using a false discovery rate cutoff of Q = 0.30, 1,138 genes at baseline and 680 genes at 36 months significantly correlated with total erosions. No evidence of a signal differentiating disease progression, or change in erosion scores between baseline and 36 months, was found. Further analyses demonstrated that the differential gene expression signature was localized to the patients with the most erosive disease (>10 erosions). Ingenuity Pathway Analysis demonstrated that genes with fold change greater than 1.5 implicated immune pathways such as CTLA signaling in cytotoxic T lymphocytes. These results demonstrate that CLEAR patients with early RA having the most severe erosive disease, as compared to more mild cases (<10 erosions), may be characterized by a set of differentially expressed genes that represent biological pathways with relevance to autoimmune disease.
KeywordsGenome-wide gene expression Sharp/van der Heijde Pathway analysis CLEAR ABCoN
The authors kindly thank the CLEAR investigators: Moreland, Conn, Smith, Callahan, Jonas, Brasington, Howard. This research was supported by NIH 2P60 AR048095-06 (RP Kimberly, P.I.) Multidisciplinary Clinical Research Center Project 3: Predictors of Rheumatoid Arthritis Severity in African Americans; and NIH N01-AR-6-2278 (SLB, PI) Continuation of the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry. Support also provided by the UAB Center for Clinical and Translational Science through the NIH National Center for Research Resources as part of its Clinical and Translational Science Award Program (5UL1RR025777-03, 5KL2RR025776-03, 5TL1RR025775-03). RJR was supported in part by NIH K01- AR060848 and LKV by K01-DK080188. The authors gratefully acknowledge the kind willingness of the CLEAR study participants whose PBMCs were used for this study.
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