Vol.23 No.4

Original Article

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

Authors

Kyle A. Serikawa 1 , S?ren Jacobsen2 , Dorthe Lundsgaard3 , Brian A. Fox1 , Lone Hummelshoj4 , Lars K. Poulsen4 , Jan Fleckner3 , Klaus Stensgaard Frederiksen3

  • Novo Nordisk Inflammation Research Center, 530 Fairview Ave N, Seattle, WA 98109, USA
  • Department of Rheumatology, Copenhagen University Hospital, Copenhagen, Denmark
  • Novo Nordisk A/S, Novo Nordisk Park, 2760 M?l?v, Denmark
  • Laboratory for Medical Allergology, Allergy Clinic, Copenhagen University Hospital, Copenhagen, Denmark
Received:

29 March 2012

Accepted:

2 July 2012

Published online:

8 August 2012

Full Text

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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.

Key words

Abatacept, Infliximab, Interferon signature, Microarray, Rheumatoid arthritis, Tocilizumab