Prediction of Disease Severity in Patients with Early Rheumatoid Arthritis by Gene Expression Profiling
- Zheng Liu zheng.liu{at}mail.utexas.edu1,2
- Tuulikki Sokka tuulikki.sokka{at}ksshp.fi1,3
- Kevin Maas khmaas{at}stanford.edu1,2
- Nancy J. Olsen nancy.olsen{at}utsouthwestern.edu4
- Thomas M. Aune tom.aune{at}vanderbilt.edu1,2
- 1Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
- 2Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
- 3Jyväskylä Central Hospital, 40620 Jyväskylä, Finland
- 4Division of Rheumatic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX 75390, USA
Abstract
In order to test the ability of peripheral blood gene expression profiles to predict future disease severity in patients with
early rheumatoid arthritis (RA), a group of 17 patients ( years disease duration) was evaluated at baseline for gene expression profiles. Disease status was evaluated after a mean
of 5 years using an index combining pain, global and recoded MHAQ scores. Unsupervised and supervised algorithms identified
“predictor genes” whose combined expression levels correlated with follow-up disease severity scores. Unsupervised clustering
algorithms separated patients into two branches. The only significant difference between these two groups was the disease
severity score; demographic variables and medication usage were not different. Supervised T-Test analysis identified 19 “predictor genes” of future disease severity. Results were validated in an independent cohort
of subjects of established RA with using Support Vector Machines and K-Nearest-Neighbor Classification. Our study demonstrates
that peripheral blood gene expression profiles may be a useful tool to predict future disease severity in patients with early
and established RA.
- Received July 27, 2008.
- Revision received December 16, 2008.
- Accepted March 11, 2009.
- © 2009 Zheng Liu et al.