Gene expression profiling in autoimmune diseases: Chronic inflammation or disease specific patterns?

Abstract

A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant differences in peripheral blood mononuclear cell (MNC) gene expression patterns between 15 newly diagnosed HT patients and 15 matched healthy controls. However, the MNC expression levels of five genes were significantly upregulated in 25 IBD patients, compared to 18 matched healthy controls (CD14, FACL2, FCN1, RNASE2, VNN2). There was concordance in the directional change for all genes between IBD and RA patients, i.e. increased expression compared to controls. These data show that one third of the genes significantly upregulated in MNC from RA patients were upregulated in patients with other chronic immunoinflammatory diseases, but only if accompanied by pronounced systemic manifestations. This suggests that at least some of the genes activated in RA are predominantly or solely related to general and disease-nonspecific autoimmune processes.

• Gene expression
• rheumatoid arthritis
• inflammatory bowel disease
• chronic autoimmune thyroiditis
• autoimmunity
• chronic inflammation

Acknowledgements

This work was supported by grants from the Danish Biotechnology Program, the Danish Medical Research Council and the Novo Nordisk Foundation. The authors wish to thank Pia G. Meinke and Nanna Bøgesvang for excellent technical assistance and Dr Klaus Rieneck for critical review of the manuscript.