OBJECTIVE: To characterise activation of the type I interferon (IFN) pathway in 
patients with systemic lupus erythematosus (SLE), dermatomyositis (DM), 
polymyositis (PM), rheumatoid arthritis (RA) and systemic scleroderma (SSc) and 
to evaluate the potential to develop a molecular diagnostic tool from the 
peripheral blood that reflects this activation in disease-affected tissues.
METHODS: Overexpressed transcripts were identified in the whole blood (WB) of 
262 patients with SLE, 44 with DM, 33 with PM, 28 with SSc and 89 with RA and 
compared with 24 healthy subjects using Affymetrix microarrays. A five gene type 
I IFN signature was assessed in these subjects to identify subpopulations 
showing both activation and concordance of the type I IFN pathway in the 
peripheral blood and disease-affected tissues of each disease and to correlate 
activation of this pathway in the WB with clinical measurements.
RESULTS: A common set of 36 type I IFN inducible transcripts were identified 
among the most overexpressed in the WB of all subjects. Significant activation 
of the type I IFN pathway in subgroups of each of the five diseases studied was 
observed. Baseline disease activity measurements correlated with a type I IFN 
gene signature in the WB of subjects with SLE, PM and SSc, as did various serum 
autoantibody levels in subjects with SLE and DM. This signature was also well 
correlated between disease-affected tissue and WB in subjects with SLE, DM, PM 
and SSc.
CONCLUSIONS: The results indicate that the type I IFN pathway is activated in 
patient subsets of five rheumatic diseases and suggest that these subsets may 
benefit from anti-IFN therapy.