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Pharmacogenomics of infliximab treatment using peripheral blood cells of patients with rheumatoid arthritis

Genes & Immunity volume 11, pages 622–629 (2010)Cite this article

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Abstract

To provide insight into the pharmacological changes in the peripheral blood (PB) molecular profile induced by tumor necrosis factor (TNF)-blockade in patients with rheumatoid arthritis (RA), blood was obtained in PAXgene tubes from 33 RA patients before and 1 month after TNF-blocking therapy (infliximab). From 15 randomly chosen patients pre- and post-treatment gene expression profiles were determined. The remaining 18 RA patients served as validation cohort. A group-based paired analysis of the gene expression profiles from the post- vs pre-treatment samples revealed a signature of genes significantly regulated by TNF-blockade. Downregulated genes reflected several biological pathways such as inflammation, angiogenesis, B- and T-cell activation. Further analysis revealed that the pharmacological response signature was significantly regulated in all treated patients, irrespective of clinical response, which is indicative for the presence of an active TNF pathway in all RA patients. The data imply that all patients carried features of TNF bioactivity irrespective of clinical response. These results favor a model for the parallel presence of TNF-dependent and TNF-independent pathways in the individual RA patient. Clinical response status to TNF-blockade may be dependent on the relative contribution of TNF-independent effector pathways.

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Acknowledgements

This study was supported by a grant from 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 European Community's FP6 funding (Autocure), the Innovation Oriented research Program (IOP) on Genomics and the Centre for Medical Systems Biology (The Netherlands Genomics Initiative). 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. L G M van Baarsen

    Present address: 5Current address: Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.,

  2. L G M van Baarsen and C A Wijbrandts: These authors contributed equally to this work.

Authors and Affiliations

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

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

  2. Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands,

    C A Wijbrandts, D M Gerlag & P P Tak

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

    T C T M van der Pouw Kraan

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

    B A C Dijkmans & C L Verweij

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  1. L G M van Baarsen
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Correspondence to C L Verweij.

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Competing interests

PP Tak has served as a consultant for Abbott, Amgen, Centocor, Schering-Plough, UCB and Wyeth.

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van Baarsen, L., Wijbrandts, C., Gerlag, D. et al. Pharmacogenomics of infliximab treatment using peripheral blood cells of patients with rheumatoid arthritis. Genes Immun 11, 622–629 (2010). https://doi.org/10.1038/gene.2010.34

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  • DOI: https://doi.org/10.1038/gene.2010.34

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