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Discovery of distinctive gene expression profiles in rheumatoid synovium using cDNA microarray technology: evidence for the existence of multiple pathways of tissue destruction and repair

Genes & Immunity volume 4, pages 187–196 (2003)Cite this article

Abstract

Rheumatoid arthritis (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria.

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Acknowledgements

We are grateful to Drs Patrick O. Brown and David Botstein in whose laboratories most of the work described in this report was performed. The work carried out in Patrick O. Brown's lab was supported by the Howard Huges Medical Institute and a grant from the NCI.

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Authors and Affiliations

  1. Department of Molecular Cell Biology, VU University Medical Center, Amsterdam, The Netherlands

    T C T M van der Pouw Kraan & C L Verweij

  2. Department of Rheumatology, Leiden University Medical Center, The Netherlands

    F A van Gaalen, T W J Huizinga, E Pieterman & F C Breedveld

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  1. T C T M van der Pouw Kraan
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  2. F A van Gaalen
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  3. T W J Huizinga
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  4. E Pieterman
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  6. C L Verweij
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Corresponding author

Correspondence to T C T M van der Pouw Kraan.

Additional information

This study was financially supported in part by the Howard Hughes Medical Institute, a grant from the National Cancer Institute, a research grant from The Netherlands Organization for Scientific Research and the Dutch Arthritis Association.

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van der Pouw Kraan, T., van Gaalen, F., Huizinga, T. et al. Discovery of distinctive gene expression profiles in rheumatoid synovium using cDNA microarray technology: evidence for the existence of multiple pathways of tissue destruction and repair. Genes Immun 4, 187–196 (2003). https://doi.org/10.1038/sj.gene.6363975

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