Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Relationship Between Disease Activity and Type 1 Interferon- and Other Cytokine-Inducible Gene Expression in Blood in Dermatomyositis and Polymyositis
Greenberg1, Steven A., Higgs2, Brandon W., Morehouse2, Christopher, Brohawn2, Philip, Zhu2, Wei, Walsh1, Ronan J., Kong1, Sek Won
A longitudinal study evaluated a group of cytokines including type 1 interferon (IFN) that are potentially involved in the pathogenesis of dermatomyositis (DM) and polymyositis (PM) pathogenesis before and during treatment. Peripheral blood of 42 patients with DM or PM was subjected to gene expression profiling using Affymetrix human genome U133 plus 2.0 GeneChips® in an initial study to identify the prevalence of patients exhibiting periphery overexpression of type 1 IFN-inducible genes. To gain further scientific insight on type 1 IFN as a potential therapeutic target for DM and PM, 24 patients with DM or PM were then prospectively enrolled and followed for up to 6 years (mean of 1.9 years) while receiving standard clinical care.
Clinical courses including MITAX scoring of disease activity were assessed across 150 patient visits. Peripheral blood samples collected at 80 patient visits were used for microarray analysis of, GM-CSF,b, IL-1acytokine-induced gene expression for type 1 IFN, TNF- IL-10, and IL-13 signaling pathways.
35 of 42 (87%) DM and PM patients had moderate/strong overexpression of type 1 IFN-inducible genes in the periphery blood. In the longitudinal study during the course of treatment, 21 of 24 patients showed overexpression of a type 1 IFN-inducible gene signature in peripheral blood. Overexpression of type 1 IFN-inducible genes IFI27, IFI44, IFI44L, and RSAD2 and a type 1 IFN-inducible 13-gene composite signature correlated highly with disease activity during treatment. For 3 patients, type 1 IFN-inducible gene overexpression during treatment preceded disease, GM-CSF, IL-10, andb, IL-1arelapse within approximately 1 month. TNF- IL-13 inducible gene signatures were also overexpressed in DM and PM patients but were not correlated with disease activity.
Targeting type 1 IFN is likely to provide clinical benefit in DM and PM patient populations with overexpression of type 1 IFN-inducible genes in the periphery. Type 1 IFN-inducible gene overexpression in the periphery blood merits further study for use as a pharmacodynamic and predictive biomarker for developing anti-type 1 IFN therapy for these patients.
To cite this abstract, please use the following information:
Greenberg, Steven A., Higgs, Brandon W., Morehouse, Christopher, Brohawn, Philip, Zhu, Wei, Walsh, Ronan J., et al; Relationship Between Disease Activity and Type 1 Interferon- and Other Cytokine-Inducible Gene Expression in Blood in Dermatomyositis and Polymyositis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :587