Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease.
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.
Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University Hospital, Sölvegatan 23, Lund, Sweden. christian.lood@med.lu.se
Christian
C
Lood
Stefan
S
Amisten
Birgitta
B
Gullstrand
Andreas
A
Jönsen
Maria
M
Allhorn
Lennart
L
Truedsson
Gunnar
G
Sturfelt
David
D
Erlinge
Anders A
AA
Bengtsson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014652:Vascular Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000099192:CD69 Antigens
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D007370:Interferon Type I; D037181:Lectins, C-Type; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D000099192:CD69 Antigens; C104647:PRKRA protein, human; C062010:leu-13 antigen