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人类白细胞抗原I类等位基因与结节病患者的病程

Human leukocyte antigen class I alleles and the disease course in sarcoidosis patients.

作者信息

Grunewald Johan, Eklund Anders, Olerup Olle

机构信息

Department of Medicine, Division of Respiratory Medicine, Karolinska Hospital, Stockholm, Sweden.

出版信息

Am J Respir Crit Care Med. 2004 Mar 15;169(6):696-702. doi: 10.1164/rccm.200303-459OC. Epub 2003 Dec 4.

Abstract

Several lines of evidence suggest a genetic predisposition to sarcoidosis, and strong associations have been shown with the major histocompatibility complex gene complex. In this study on Scandinavian sarcoidosis patients, we investigated any influence on the outcome of disease by human leukocyte antigen (HLA) class I alleles alone and in combination with selected class II alleles. HLA-B07 independently increased the risk for persistent sarcoidosis (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.0-3.7), as well as for resolving disease (OR, 2.7; CI, 1.1-6.2), suggesting an influence on factors common to both forms of sarcoidosis. The common allele combination A03, B07, DRB115 was most strongly associated with persistent disease (OR, 4.7; CI, 2.2-10.2) and was found in 25.3% of patients with persistent disease versus 7.1% of healthy control subjects. HLA-B08 tended to increase separately the risk for resolving disease (OR, 2.4; CI, 0.7-8.0), as well as for persistent disease (OR, 2.2; CI, 0.8-6.1). Other HLA class I associations were mainly secondary to their linkages to DRB103 and DRB1*15, respectively. The influence of HLA class I alleles on sarcoidosis thus seems more pronounced than previously thought, and both HLA class I and class II should be relevant to evaluate in the clinical management of sarcoidosis patients.

摘要

多项证据表明结节病存在遗传易感性,并且已显示与主要组织相容性复合体基因复合体有密切关联。在这项针对斯堪的纳维亚结节病患者的研究中,我们单独研究了人类白细胞抗原(HLA)I类等位基因以及与选定的II类等位基因组合对疾病转归的影响。HLA - B07独立增加了结节病持续存在的风险(优势比[OR],1.9;95%置信区间[CI],1.0 - 3.7),以及疾病缓解的风险(OR,2.7;CI,1.1 - 6.2),这表明其对两种结节病形式共有的因素有影响。常见的等位基因组合A03、B07、DRB115与疾病持续存在的关联最为强烈(OR,4.7;CI,2.2 - 10.2),在25.3%的疾病持续存在患者中发现该组合,而在健康对照受试者中为7.1%。HLA - B08倾向于分别增加疾病缓解的风险(OR,2.4;CI,0.7 - 8.0)以及疾病持续存在的风险(OR,2.2;CI,0.8 - 6.1)。其他HLA I类关联主要分别继发于它们与DRB103和DRB1*15的连锁关系。因此,HLA I类等位基因对结节病的影响似乎比以前认为的更为显著,并且在结节病患者的临床管理中,HLA I类和II类都应进行评估。

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