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.