Abstract

Collagen-induced arthritis (CIA) is an experimental arthritis model used to study the inflammatory processes in this disease and test potential therapeutics. In order to better characterize this model, we conducted the first comprehensive gene expression analysis of rat CIA. To evaluate how closely the rat model reflects human rheumatoid arthritis (RA), we also analysed gene expression in human RA, using genome-wide Affymetrix gene arrays. By applying multiple strategies, including comparison of the highest induced genes, expression of immunological-associated genes as well as Ingenuity Pathway Analysis (IPA), we were able to compare the two expression profiles. Among the highest induced genes in RA were several B-cell-associated genes, including immunoglobulins, B-cell markers such as CD20, and cytokines and chemokines that act on B cells such as TNFSF13b/BLyS and CXCL13, none of which was upregulated in CIA. The latter was instead characterized by the upregulation of genes expressed primarily in macrophages and dendritic cells. Of the 22 pathways identified as significant in both diseases by IPA, only three (IL6, chemokine signalling and antigen presentation) were present in both settings. We conclude that there are significant differences in the inflammatory mechanisms between human RA and rat CIA, and that genome-wide comparative gene expression analyses are useful tools to evaluate the relevance of animal models to human disease.