Rossman Milton D, Stubbs Jose, Lee Chung Wha, Argyris Elias, Magira Eleni, Monos Dimitri
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Am J Respir Crit Care Med. 2002 Mar 15;165(6):788-94. doi: 10.1164/ajrccm.165.6.2104002.
Chronic beryllium disease (CBD) is a hypersensitivity granulomatosis characterized by beryllium hypersensitivity (BH) and mediated by CD4+ T cells. However, all individuals with BH may not develop CBD. To examine the role of the three different human leukocyte antigen (HLA) Class II isotypes in BH with (CBD) and without clinical disease (BHWCD), we performed DNA-based typing of HLA-DPB1, HLA-DQB1, and HLA-DRB1 loci on 55 subjects with BH (25 with established CBD and 30 with BHWCD), and compared this with the results for 82 beryllium-exposed workers with no evidence of BH. The allele distribution was utilized to identify candidate amino acid epitopes that differed between the study groups. HLA-DPB1-E69 was the most important marker for BH, and did not differentiate BHWCD from CBD. A significant association with CBD was observed with HLA-DQB1-G86 (p(corr) < 0.04), and HLA-DRB1-S11 was significantly increased in CBD as compared with BHWCD (p < 0.03). These observations suggest that HLA-DPB1-E69 is a marker for susceptibility to BH and not just a progression marker for CBD. In addition, HLA amino acid epitopes on HLA-DRB1 and -DQB1, in concert with or independently of HLA-DPB1-E69, may be associated with progression to CBD.
慢性铍病（CBD）是一种以铍超敏反应（BH）为特征、由CD4 + T细胞介导的超敏性肉芽肿病。然而，并非所有有BH的个体都会发展为CBD。为了研究三种不同的人类白细胞抗原（HLA）II类同种型在伴有临床疾病（CBD）和无临床疾病（BHWCD）的BH中的作用，我们对55例有BH的受试者（25例确诊为CBD，30例为BHWCD）进行了HLA-DPB1、HLA-DQB1和HLA-DRB1基因座的DNA分型，并将其与82例无BH证据的铍暴露工人的结果进行比较。利用等位基因分布来识别研究组之间不同的候选氨基酸表位。HLA-DPB1-E69是BH最重要的标志物，不能区分BHWCD和CBD。观察到HLA-DQB1-G86与CBD有显著相关性（p（校正）<0.04），与BHWCD相比，HLA-DRB1-S11在CBD中显著增加（p <0.03）。这些观察结果表明，HLA-DPB1-E69是BH易感性的标志物，而不仅仅是CBD的进展标志物。此外，HLA-DRB1和-DQB1上的HLA氨基酸表位，与HLA-DPB1-E69协同或独立作用，可能与进展为CBD有关。
