Modern Rheumatology

, Volume 23, Issue 4, pp 729–740 | Cite as

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

  • Kyle A. Serikawa
  • Søren Jacobsen
  • Dorthe Lundsgaard
  • Brian A. Fox
  • Lone Hummelshoj
  • Lars K. Poulsen
  • Jan Fleckner
  • Klaus Stensgaard Frederiksen
Original Article

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.

Keywords

Abatacept Infliximab Interferon signature Microarray Rheumatoid arthritis Tocilizumab 

Supplementary material

10165_2012_723_MOESM1_ESM.doc (140 kb)
Supplementary material 1 (DOC 140 kb)
10165_2012_723_MOESM2_ESM.xls (127 kb)
Supplementary material 2 (XLS 127 kb)
10165_2012_723_MOESM3_ESM.docx (15 kb)
Supplementary material 3 (DOCX 14 kb)

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Copyright information

© Japan College of Rheumatology 2012

Authors and Affiliations

  • Kyle A. Serikawa
    • 1
  • Søren Jacobsen
    • 2
  • Dorthe Lundsgaard
    • 3
  • Brian A. Fox
    • 1
  • Lone Hummelshoj
    • 4
  • Lars K. Poulsen
    • 4
  • Jan Fleckner
    • 3
  • Klaus Stensgaard Frederiksen
    • 3
  1. 1.Novo Nordisk Inflammation Research CenterSeattleUSA
  2. 2.Department of RheumatologyCopenhagen University HospitalCopenhagenDenmark
  3. 3.Novo Nordisk A/SMåløvDenmark
  4. 4.Laboratory for Medical Allergology, Allergy ClinicCopenhagen University HospitalCopenhagenDenmark

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