In adult onset myositis, the presence of interstitial lung disease and myositis specific/associated antibodies are governed by HLA class II haplotype, rather than by myositis subtype
In adult onset myositis, the presence of interstitial lung disease and myositis specific/associated antibodies are governed by HLA class II haplotype, rather than by myositis subtype
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DOI：
10.1186/ar1862
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发表时间：
2006-01-01
影响因子：
4.9
通讯作者：
Cooper, RG
中科院分区：
文献类型：
--
作者：
Chinoy, H;Salway, F;Cooper, RG
本研究的目的是探讨HLA II类与多发性肌炎（PM）和皮肌炎（DM）的相关性，并确定这些相关性如何影响临床和血清学差异。从225名英国白人特发性炎性肌病患者（PM = 117, DM = 108）中获得DNA样本，并与随机选择的537名英国白人对照进行比较。所有病例还被评估是否存在相关的恶性肿瘤和间质性肺疾病（ILD），以及一些肌炎特异性/肌炎相关抗体（msa /MAAs）。对受试者进行HLA-DRB1、DQA1和DQB1基因分型。HLA-DRB1*03， DQA1*05和DQB1*02与PM和DM的风险增加相关。HLA-DRB1*03-DQA1*05-DQB1*02单倍型与ILD有很强的相关性，与肌炎亚型或是否存在抗氨基酰基转移RNA合成酶抗体无关。HLA-DRB1*07-DQA1*02- dqb1 *02单倍型与抗mi -2抗体风险相关，即使在抗mi -2阴性患者中也能区分PM和DM（优势比为0.3,95%置信区间为0.1 - 0.6）。其他MSA/MAAs显示与其他HLA II类单倍型特异性相关，与肌炎亚型无关。与恶性肿瘤无基因型、单倍型或血清学相关性。HLA-DRB1*03-DQA1*05-DQB1*02单倍型关联不仅决定了高加索PM/DM患者的疾病易感性，而且还决定了PM/DM的共同表型特征。HLA-DRB1*07-DQA1*02- dqb1 *02单倍型虽然与抗mi -2抗体密切相关，但与PM/DM疾病易感性存在差异相关性。总之，这些发现支持这样一种观点，即不同血清学的肌炎患者具有不同的免疫遗传谱，这些谱可以定义特定的肌炎亚型。
The aim of this study was to investigate HLA class II associations in polymyositis (PM) and dermatomyositis (DM), and to determine how these associations influence clinical and serological differences. DNA samples were obtained from 225 UK Caucasian idiopathic inflammatory myopathy patients (PM = 117, DM = 108) and compared with 537 randomly selected UK Caucasian controls. All cases had also been assessed for the presence of related malignancy and interstitial lung disease (ILD), and a number of myositis-specific/myositis-associated antibodies (MSAs/MAAs). Subjects were genotyped for HLA-DRB1, DQA1 and DQB1. HLA-DRB1*03, DQA1*05 and DQB1*02 were associated with an increased risk for both PM and DM. The HLA-DRB1*03-DQA1*05-DQB1*02 haplotype demonstrated strong association with ILD, irrespective of myositis subtype or presence of anti-aminoacyl-transfer RNA synthetase antibodies. The HLA-DRB1*07-DQA1*02-DQB1*02 haplotype was associated with risk for anti-Mi-2 antibodies, and discriminated PM from DM (odds ratio 0.3, 95% confidence interval 0.1 - 0.6), even in anti-Mi-2 negative patients. Other MSA/MAAs showed specific associations with other HLA class II haplotypes, irrespective of myositis subtype. There were no genotype, haplotype or serological associations with malignancy. The HLA-DRB1*03-DQA1*05-DQB1*02 haplotype associations appear to not only govern disease susceptibility in Caucasian PM/DM patients, but also phenotypic features common to PM/DM. Though strongly associated with anti-Mi-2 antibodies, the HLA-DRB1*07-DQA1*02-DQB1*02 haplotype shows differential associations with PM/DM disease susceptibility. In conclusion, these findings support the notion that myositis patients with differing myositis serology have different immunogenetic profiles, and that these profiles may define specific myositis subtypes.