Department of Medicine, Rheumatology Unit, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden.
Ann Rheum Dis. 2013 Jun;72(6):1018-25. doi: 10.1136/annrheumdis-2012-201760. Epub 2012 Aug 14.
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.
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.
HLA-DRB104 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB113 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-DRB104-while HLA-DRB113 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.
The HLA-DRB104 and HLA-DRB113 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.
血管疾病在系统性红斑狼疮（SLE）中很常见，抗磷脂抗体（aPL）阳性的患者发生动脉和静脉血栓的风险很高。由于 HLA Ⅱ类基因型与促血栓形成的 aPL 有关，我们研究了 HLA-DRB1 等位基因、aPL 与 SLE 患者血管事件之间的关系。
纳入 665 名白种人来源的 SLE 患者和 1403 名对照者。记录缺血性心脏病、缺血性脑血管病（ICVD）和静脉血栓栓塞症（统称为任何血管事件（AVE））的既往表现。使用 ELISA 法检测 aPL。采用序列特异性引物-PCR 对 HLA-DRB1 进行两位数字分型。
与未受影响的患者相比，ICVD 的 SLE 患者 HLA-DRB104 更为常见。在调整了已知的传统心血管危险因素后，这种相关性仍然存在。HLA-DRB113 与 AVE 相关。所有测量的 aPL-抗心磷脂 IgG 和 IgM、β2-糖蛋白-1 IgG、凝血酶原（PT）IgG 和狼疮抗凝剂试验阳性均与 HLA-DRB104 相关-而 HLA-DRB113 与 IgG 抗体（β2-糖蛋白-1、抗心磷脂和 PT）相关。在具有联合风险等位基因 HLA-DRB1*04/*13 的患者中，AVE 和 ICVD 的结局存在显著的相加交互作用。
HLA-DRB104 和 HLA-DRB113 等位基因与 SLE 中的血管事件和 aPL 阳性免疫表型相关。结果表明，SLE 患者的一个亚群具有遗传倾向的血管脆弱性。
