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Expression of a pathogen-response program in peripheral blood cells defines a subgroup of Rheumatoid Arthritis patients

Genes & Immunity volume 9, pages 16–22 (2008)Cite this article

Abstract

Rheumatoid arthritis (RA) is a heterogeneous disease with unknown etiology. Here we aimed to distinguish RA subtypes based on peripheral blood (PB) gene expression profiles in comparison with a pathogen-response transcriptional program. PB was obtained from 35 RA patients and 15 healthy individuals. For expression profiling we used DNA microarrays. A combined cluster analysis of RA and control samples together with samples from a viral infection model revealed that the gene expression profile of a subgroup of RA patients (RAA) was reminiscent to that of poxvirus-infected macaques. Statistical analysis, followed by Gene Ontology analysis of the RAA patients confirmed that these patients form a distinct group, with activation of several host defense mechanisms that resemble a common host-pathogen response. Analysis of the promoter region of genes that were overexpressed in the RAA patients, revealed an enrichment of transcription factor binding sites for NFκB and interferon-activated transcription factors. Moreover, this subgroup of RA patients expressed significantly increased titers of anti-cyclic citrullinated peptide antibodies. We conclude that activation of a host-pathogen response defines a subgroup of RA patients characterized by increased autoreactivity against citrullinated proteins.

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Acknowledgements

We would like to thank the following authors for making their microarray data publicly available: RG Jenner (Cambridge, USA) and KH Rubins (Stanford, USA). This study was supported in part by the EURO-RA Marie Curie Trainings network, the European Community's FP6 funding (Autocure), the Netherlands Organization for Health Research and Development (ZonMw) in assignment of the Netherlands Organization for Scientific Research (NWO, grant number 945-02-029), the Innovation Oriented research Program (IOP) on Genomics and Centre for Medical Systems Biology (a center of excellence approved by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research). This publication reflects only the authors' views. The European Community is not liable for any use that may be made of the information herein.

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Author notes

  1. T C T M van der Pouw Kraan and L G M van Baarsen: These authors contributed equally to this study.

Authors and Affiliations

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

    T C T M van der Pouw Kraan, L G M van Baarsen, F Rustenburg, J M Baggen & C L Verweij

  2. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

    L G M van Baarsen, F Rustenburg & C L Verweij

  3. Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    C A Wijbrandts & P P Tak

  4. Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands

    A E Voskuyl & B A C Dijkmans

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  1. T C T M van der Pouw Kraan
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Correspondence to T C T M van der Pouw Kraan.

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van der Pouw Kraan, T., van Baarsen, L., Wijbrandts, C. et al. Expression of a pathogen-response program in peripheral blood cells defines a subgroup of Rheumatoid Arthritis patients. Genes Immun 9, 16–22 (2008). https://doi.org/10.1038/sj.gene.6364438

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