Newman Taylor A J, Cullinan P, Lympany P A, Harris J M, Dowdeswell R J, du Bois R M
Department of Occupational and Environmental Medicine, Imperial College School of Medicine (National Heart and Lung Institute), London, United Kingdom.
Am J Respir Crit Care Med. 1999 Aug;160(2):435-8. doi: 10.1164/ajrccm.160.2.9807065.
The development of sensitization to inhaled allergens is determined by the interaction of multiple genetic and environmental influences. Occupational sensitization to low-molecular-weight chemicals allows a specific immunological response to an inhaled hapten to be studied in a well-defined population with characterized exposure. We investigated the workforce of a large platinum refinery exposed to ammonium hexachloroplatinate (ACP) to test the hypothesis that the development of IgE-associated sensitization to ACP was influenced by human leukocyte-associated antigen (HLA) phenotype, especially in those with lower ACP exposure. We performed HLA typing in 44 cases with a positive skin prick test to ACP, and 57 nonsensitized referents matched on age, race, duration of employment, and category of ACP exposure. An HLA-DR3 phenotype was more common among cases (odds ratio [OR] 2.3), and more so in those with low (OR infinite) than with high exposure (OR 1.6); HLA-DR6 was less common among the cases (OR 0.4), an association also stronger in the low-exposure group (OR 0.1 versus 0.5). These results provide evidence that HLA phenotype is a significant determinant of sensitization to complex platinum salts and for the first time show that the strength of this association varies with intensity of exposure to the sensitizing agent. They imply that as exposure-control measures are taken to prevent occupational sensitization and, by analogy, sensitization to allergens outside the workplace, disease incidence will increasingly be determined by genetic susceptibility.
对吸入性变应原的致敏作用发展取决于多种遗传和环境因素的相互作用。对低分子量化学物质的职业致敏作用使人们能够在暴露特征明确的特定人群中研究对吸入性半抗原的特异性免疫反应。我们调查了一家大型铂精炼厂中接触六氯铂酸铵（ACP）的工人，以检验以下假设：对ACP的IgE相关致敏作用的发展受人类白细胞相关抗原（HLA）表型的影响，尤其是在那些ACP暴露量较低的工人中。我们对44例ACP皮肤点刺试验呈阳性的病例以及57例在年龄、种族、工作年限和ACP暴露类别方面相匹配的未致敏对照者进行了HLA分型。HLA-DR3表型在病例中更为常见（优势比[OR]为2.3），在低暴露组（OR无穷大）中比高暴露组（OR为1.6）更常见；HLA-DR6在病例中较少见（OR为0.4），在低暴露组中的关联也更强（OR为0.1对0.5）。这些结果提供了证据，表明HLA表型是对复杂铂盐致敏的重要决定因素，并且首次表明这种关联的强度随致敏剂暴露强度而变化。它们意味着，随着采取暴露控制措施来预防职业致敏作用，并且以此类推预防工作场所以外的变应原致敏作用，疾病发病率将越来越多地由遗传易感性决定。
