RT Journal Article
SR Electronic
T1 HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1018
OP 1025
DO 10.1136/annrheumdis-2012-201760
VO 72
IS 6
A1 Lundström, Emeli
A1 Gustafsson, Johanna T
A1 Jönsen, Andreas
A1 Leonard, Dag
A1 Zickert, Agneta
A1 Elvin, Kerstin
A1 Sturfelt, Gunnar
A1 Nordmark, Gunnel
A1 Bengtsson, Anders A
A1 Sundin, Ulf
A1 Källberg, Henrik
A1 Sandling, Johanna K
A1 Syvänen, Ann-Christine
A1 Klareskog, Lars
A1 Gunnarsson, Iva
A1 Rönnblom, Lars
A1 Padyukov, Leonid
A1 Svenungsson, Elisabet
YR 2013
UL http://ard.bmj.com/content/72/6/1018.abstract
AB 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, β2-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 (β2-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.