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Detection of gene expression signatures related to underlying disease and treatment in rheumatoid arthritis patients

  • Original Article
  • Published:
Modern Rheumatology

An Erratum to this article was published on 05 October 2012

Abstract

Objectives

Gene expression signatures can provide an unbiased view into the molecular changes underlying biologically and medically interesting phenotypes. We therefore initiated this study to identify signatures that would be of utility in studying rheumatoid arthritis (RA).

Methods

We used microarray profiling of peripheral blood mononuclear cells (PBMCs) in 30 RA patients to assess the effect of different biologic agent (biologics) treatments and to quantify the degree of a type-I interferon (IFN) signature in these patients. A numeric score was derived for the quantification step and applied to patients with RA. To further characterize the IFN response in our cohort, we employed type-I IFN treatment of PBMCs in vitro and in reporter assays.

Results

Profiling identified a subset of RA patients with upregulation of type-I IFN-regulated transcripts, thereby corroborating previous reports showing RA to be heterogeneous for an IFN component. A comparison of individuals currently untreated with a biologic with those treated with infliximab, tocilizumab, or abatacept suggested that each biologic induces a specific gene signature in PBMCs.

Conclusions

It is possible to observe signs of type-I IFN pathway activation in a subset of clinically active RA patients without C-reactive protein elevation. Furthermore, biologics-specific gene signatures in patients with RA indicate that looking for a biologic-specific response pattern may be a potential future tool for predicting individual patient response.

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Conflict of interest

The authors declare that they have no conflict of interest with respect to the work reported here.

Author information

Authors and Affiliations

  1. Novo Nordisk Inflammation Research Center, 530 Fairview Ave N, Seattle, WA, 98109, USA

    Kyle A. Serikawa & Brian A. Fox

  2. Department of Rheumatology, Copenhagen University Hospital, Copenhagen, Denmark

    Søren Jacobsen

  3. Novo Nordisk A/S, Novo Nordisk Park, 2760, Måløv, Denmark

    Dorthe Lundsgaard, Jan Fleckner & Klaus Stensgaard Frederiksen

  4. Laboratory for Medical Allergology, Allergy Clinic, Copenhagen University Hospital, Copenhagen, Denmark

    Lone Hummelshoj & Lars K. Poulsen

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  1. Kyle A. Serikawa
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Correspondence to Kyle A. Serikawa.

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Serikawa, K.A., Jacobsen, S., Lundsgaard, D. et al. Detection of gene expression signatures related to underlying disease and treatment in rheumatoid arthritis patients. Mod Rheumatol 23, 729–740 (2013). https://doi.org/10.1007/s10165-012-0723-9

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  • DOI: https://doi.org/10.1007/s10165-012-0723-9

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