Patients with systemic lupus erythematosus (SLE) have a markedly increased risk 
to develop cardiovascular disease, and traditional cardiovascular risk factors 
fail to account for this increased risk. We used microarray to probe the 
platelet transcriptome in patients with SLE and healthy controls, and the gene 
and protein expression of a subset of differentially expressed genes was further 
investigated and correlated to platelet activation status. Real-time PCR was 
used to confirm a type I interferon (IFN) gene signature in patients with SLE, 
and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (P < .0001) were found to 
be up-regulated in platelets from SLE patients compared with healthy volunteers. 
Notably, patients with a history of vascular disease had increased expression of 
type I IFN-regulated proteins as well as more activated platelets compared with 
patients without vascular disease. We suggest that interferogenic immune 
complexes stimulate production of IFNα that up-regulates the megakaryocytic type 
I IFN-regulated genes and proteins. This could affect platelet activation and 
contribute to development of vascular disease in SLE. In addition, platelets 
with type I IFN signature could be a novel marker for vascular disease in SLE.