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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.

Lood, Christian LU ; Amisten, Stefan LU ; Gullstrand, Birgitta LU ; Jönsen, Andreas LU ; Allhorn, Maria LU ; Truedsson, Lennart LU ; Sturfelt, Gunnar LU ; Erlinge, David LU and Bengtsson, Anders LU (2010) In Blood Jul 1. p.1951-1957
Abstract
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 individuals 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<0.0001) were found to be up-regulated in platelets from SLE patients as compared to healthy volunteers. Notably, patients with a history... (More)
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 individuals 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<0.0001) were found to be up-regulated in platelets from SLE patients as compared to 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 as compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFNalpha which 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
Jul 1
pages
1951 - 1957
publisher
American Society of Hematology
external identifiers
  • wos:000282152000021
  • pmid:20538795
  • scopus:77956905671
ISSN
1528-0020
DOI
10.1182/blood-2010-03-274605
language
English
LU publication?
yes
id
4460dd46-8d33-4b17-8116-3ad4a1c6200b (old id 1626187)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20538795?dopt=Abstract
date added to LUP
2010-07-05 10:55:21
date last changed
2018-06-03 04:30:29
@article{4460dd46-8d33-4b17-8116-3ad4a1c6200b,
  abstract     = {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 individuals 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&lt;0.0001) were found to be up-regulated in platelets from SLE patients as compared to 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 as compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFNalpha which 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.},
  author       = {Lood, Christian and Amisten, Stefan and Gullstrand, Birgitta and Jönsen, Andreas and Allhorn, Maria and Truedsson, Lennart and Sturfelt, Gunnar and Erlinge, David and Bengtsson, Anders},
  issn         = {1528-0020},
  language     = {eng},
  pages        = {1951--1957},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {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.},
  url          = {http://dx.doi.org/10.1182/blood-2010-03-274605},
  volume       = {Jul 1},
  year         = {2010},
}