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Peripheral blood gene expression profiling in rheumatoid arthritis

Genes & Immunity volume 6, pages 388–397 (2005)Cite this article

Abstract

We carried out gene expression profiling of peripheral blood mononuclear cells (PBMCs) in 29 patients with active rheumatoid arthritis (RA) and 21 control subjects using Affymetrix U95Av2 arrays. Using cluster analysis, we observed a significant alteration in the expression pattern of 81 genes (P<0.001) in the PBMCs of RA patients compared with controls. Many of these genes correlated with differences in monocyte counts between the two study populations, and we show that a large fraction of these genes are specifically expressed at high levels in monocytes. In addition, a logistic regression analysis was performed to identify genes that performed best in the categorization of RA and control samples. Glutaminyl cyclase, IL1RA, S100A12 (also known as calgranulin or EN-RAGE) and Grb2-associated binding protein (GAB2) were among the top discriminators. Along with previous data, the overexpression of S100A12 in RA patients emphasizes the likely importance of RAGE pathways in disease pathogenesis. The altered expression of GAB2, an intracellular adaptor molecule involved in regulating phosphatase function, is of particular interest given the recent identification of the intracellular phosphatase PTPN22 as a risk gene for RA. These data suggest that a detailed study of gene expression patterns in peripheral blood can provide insight into disease pathogenesis. However, it is also clear that substantially larger sample sizes will be required in order to evaluate fully gene expression profiling as a means of identifying disease subsets, or defining biomarkers of outcome and response to therapy in RA.

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Acknowledgements

We thank Leslie Goodwin and Sarah Lombardi for assistance with the microarray assays, and Jen Deng, Harini Govindarajan, V Kakkanaiah and Chris Todd for support with SurroScan assays. We also thank Robert Lundsten, Jubal Dais and Ismael Rodriquez for database support by the NSLIJHS Biorepository Informatics Group. We are grateful to Cerdi Beltre for assistance with patient recruitment, and to all the RA patients who agreed to participate in this study. This work was supported by a NIAMS contract NO1-AR-1-2256 (PKG).

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Authors and Affiliations

  1. Robert S Boas Center for Genomics and Human Genetics, North Shore-Long Island Jewish Research Institute, Manhasset, NY, USA

    F M Batliwalla, X Xiao, W Li, H Khalili, A Damle, P S Gulko, M Kern & P K Gregersen

  2. Department of Medicine, NSUH, Manhasset, NY, USA

    F M Batliwalla, X Xiao, W Li, H Khalili, A Damle, P S Gulko, M Kern, R Furie & P K Gregersen

  3. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    E C Baechler, S Balasubramanian, W A Ortmann & T W Behrens

  4. SurroMed Inc., Menlo Park, CA, USA

    A Perrone & A B Kantor

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  1. F M Batliwalla
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Correspondence to P K Gregersen.

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Supplementary information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene).

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Batliwalla, F., Baechler, E., Xiao, X. et al. Peripheral blood gene expression profiling in rheumatoid arthritis. Genes Immun 6, 388–397 (2005). https://doi.org/10.1038/sj.gene.6364209

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