MHC associations with clinical and autoantibody manifestations in European SLE.
MHC associations with clinical and autoantibody manifestations in European SLE.
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作者：
系统性红斑狼疮（SLE）是一种影响多器官系统的临床异质性疾病，其特征是对核成分形成自身抗体。虽然主要组织相容性复合体（MHC）内的遗传变异与SLE有关，但其在临床表现发展和自身抗体产生中的作用尚不明确。我们对四个独立的欧洲SLE病例进行了荟萃分析，以研究SLE亚表型与MHC单核苷酸多态性基因型、人类白细胞抗原（HLA）等位基因和HLA变异氨基酸之间的关系。在11个美国风湿病学会标准和7个自身抗体亚表型中，抗ro /SSA和抗la /SSB抗体亚群显示出最多的数量和最具统计学意义的相关性。HLA-DRB1*03:01与两种亚表型均显著相关。我们在抗ro亚群中发现了独立于MHC II类变异的关联证据。条件分析显示，抗ro和抗la亚群与HLA-DRB1*0301独立相关，HLA-DRB1*03:01与SLE的关联很大程度上但不完全是由该等位基因与这些亚表型的关联驱动的。我们的研究结果为HLA-DRB1*03:01在SLE中的多水平风险模型提供了强有力的证据，其中抗ro和抗la抗体阳性SLE的相关性比不含这些自身抗体的SLE强得多。
Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.
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影响因子：
4.5
作者：
Barcellos LF;May SL;Ramsay PP;Quach HL;Lane JA;Nititham J;Noble JA;Taylor KE;Quach DL;Chung SA;Kelly JA;Moser KL;Behrens TW;Seldin MF;Thomson G;Harley JB;Gaffney PM;Criswell LA
通讯作者：
Criswell LA
影响因子：
4.3
作者：
Dilthey, Alexander;Leslie, Stephen;McVean, Gil
通讯作者：
McVean, Gil
影响因子：
4.5
作者：
Cunninghame Graham DS;Morris DL;Bhangale TR;Criswell LA;Syvänen AC;Rönnblom L;Behrens TW;Graham RR;Vyse TJ
通讯作者：
Vyse TJ
中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
通讯作者：
Zhang, Xue-Jun
DOI：
10.1073/pnas.0909307106
发表时间：
2009-11-03
影响因子：
11.1
作者：
Rioux, John D.;Goyette, Philippe;Hauser, Stephen L.
通讯作者：
Hauser, Stephen L.