title: Detection of gene expression signatures related to underlying disease and treatment in rheumatoid arthritis patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Novo Nordisk Inflammation Research Center, 530 Fairview Ave N, Seattle, WA 98109, USA. kyse@novonordisk.com
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Serikawa
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Dorthe
authors.initials: D
authors.lastname: Lundsgaard
authors.forename: Brian A
authors.initials: BA
authors.lastname: Fox
authors.forename: Lone
authors.initials: L
authors.lastname: Hummelshoj
authors.forename: Lars K
authors.initials: LK
authors.lastname: Poulsen
authors.forename: Jan
authors.initials: J
authors.lastname: Fleckner
authors.forename: Klaus Stensgaard
authors.initials: KS
authors.lastname: Frederiksen
mesh_terms: D000069594:Abatacept; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D001688:Biological Products / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D000069285:Infliximab; D007370:Interferon Type I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D018796:Immunoconjugates; D007370:Interferon Type I; D000069594:Abatacept; D000069285:Infliximab; C502936:tocilizumab