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HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus

Lundstrom, Emeli; Gustafsson, Johanna T.; Jönsen, Andreas LU ; Leonard, Dag; Zickert, Agneta; Elvin, Kerstin; Sturfelt, Gunnar LU ; Nordmark, Gunnel; Bengtsson, Anders LU and Sundin, Ulf, et al. (2013) In Annals of the Rheumatic Diseases 72(6). p.1018-1025
Abstract
Background and objectives Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients. Methods 665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific... (More)
Background and objectives Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients. Methods 665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific primer-PCR. Results HLA-DRB1*04 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB1*13 was associated with AVE. All measured specificities of aPL-cardiolipin IgG and IgM, beta(2)-glycoprotein-1 IgG, prothrombin (PT) IgG and a positive lupus anticoagulant test were associated with HLA-DRB1*04-while HLA-DRB1*13 was associated with IgG antibodies (beta(2)-glycoprotein-1, cardiolipin and PT). In patients with the combined risk alleles, HLA-DRB1*04/*13, there was a significant additive interaction for the outcomes AVE and ICVD. Conclusions The HLA-DRB1*04 and HLA-DRB1*13 alleles are associated with vascular events and an aPL positive immune-phenotype in SLE. Results demonstrate that a subset of SLE patients is genetically disposed to vascular vulnerability. (Less)
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published
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Annals of the Rheumatic Diseases
volume
72
issue
6
pages
1018 - 1025
publisher
British Medical Association
external identifiers
  • wos:000318907100043
  • scopus:84877604619
ISSN
1468-2060
DOI
10.1136/annrheumdis-2012-201760
language
English
LU publication?
yes
id
5c9bbe89-4803-4481-a5dd-dc76cf906be3 (old id 3932471)
date added to LUP
2013-08-01 07:40:44
date last changed
2019-01-27 04:32:20
@article{5c9bbe89-4803-4481-a5dd-dc76cf906be3,
  abstract     = {Background and objectives Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients. Methods 665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific primer-PCR. Results HLA-DRB1*04 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB1*13 was associated with AVE. All measured specificities of aPL-cardiolipin IgG and IgM, beta(2)-glycoprotein-1 IgG, prothrombin (PT) IgG and a positive lupus anticoagulant test were associated with HLA-DRB1*04-while HLA-DRB1*13 was associated with IgG antibodies (beta(2)-glycoprotein-1, cardiolipin and PT). In patients with the combined risk alleles, HLA-DRB1*04/*13, there was a significant additive interaction for the outcomes AVE and ICVD. Conclusions The HLA-DRB1*04 and HLA-DRB1*13 alleles are associated with vascular events and an aPL positive immune-phenotype in SLE. Results demonstrate that a subset of SLE patients is genetically disposed to vascular vulnerability.},
  author       = {Lundstrom, Emeli and Gustafsson, Johanna T. and Jönsen, Andreas and Leonard, Dag and Zickert, Agneta and Elvin, Kerstin and Sturfelt, Gunnar and Nordmark, Gunnel and Bengtsson, Anders and Sundin, Ulf and Kallberg, Henrik and Sandling, Johanna K. and Syvanen, Ann-Christine and Klareskog, Lars and Gunnarsson, Iva and Ronnblom, Lars and Padyukov, Leonid and Svenungsson, Elisabet},
  issn         = {1468-2060},
  language     = {eng},
  number       = {6},
  pages        = {1018--1025},
  publisher    = {British Medical Association},
  series       = {Annals of the Rheumatic Diseases},
  title        = {HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus},
  url          = {http://dx.doi.org/10.1136/annrheumdis-2012-201760},
  volume       = {72},
  year         = {2013},
}