Serikawa, Kyle A3; Jacobsen, Søren6; Lundsgaard, Dorthe3; Fox, Brian A3; Hummelshoj, Lone3; Poulsen, Lars K.6; Fleckner, Jan7; Frederiksen, Klaus Stensgaard3
1 Section of Neurology, Psychiatry and Sensory Sciences, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 Section of Orthopaedics and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet5 Department of Pharmacology Pharmacotherapy, Faculty of Pharmaceutical Sciences, Københavns Universitet6 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet7 Department of Pharmacology Pharmacotherapy, Faculty of Pharmaceutical Sciences, Københavns Universitet
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.
Modern Rheumatology / the Japan Rheumatism Association, 2013, p. 729-40