Samuel George, Maier Lisa A
Robert H. Hollis Laboratory of Environmental and Occupational Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
Curr Opin Allergy Clin Immunol. 2008 Apr;8(2):126-34. doi: 10.1097/ACI.0b013e3282f824a4.
This review discusses the immunology of chronic beryllium disease. It addresses the importance of the interaction between class II molecules and the T cells that recognize beryllium, along with the subsequent immune response that results in sensitization and disease, and genetic factors leading to variation in this response.
HLA-DPB1 with a glutamic acid at amino acid position 69 (Glu69) confers increased risk of beryllium sensitization and is not specific for chronic beryllium disease. The degree of negative surface charge of the molecule may increase risk of chronic beryllium disease but not sensitization. In the absence of Glu69, HLA-DRB1 alleles may function in beryllium presentation, increasing the risk of chronic beryllium disease. The T-cell response as assessed by the beryllium lymphocyte proliferation test is dependent on central memory T-cells, while Th1 cytokine secretion leading to granulomatous inflammation and chronic beryllium disease is dependent on the activity of effector memory T cells. Polymorphisms in cytokine genes, such as the TGF-beta1 gene, also affect the risk of chronic beryllium disease and more severe disease.
The current diagnostic criteria for sensitization and chronic beryllium disease rely on the beryllium lymphocyte proliferation test. By understanding the novel immunologic mechanisms and genetic factors associated with sensitization and chronic beryllium disease, we may improve our ability to detect beryllium health effects with new diagnostics, and hopefully refine therapies for disease.
本综述探讨慢性铍病的免疫学。阐述了Ⅱ类分子与识别铍的T细胞之间相互作用的重要性，以及随之导致致敏和疾病的免疫反应，还有导致这种反应出现差异的遗传因素。
氨基酸位置69处为谷氨酸（Glu69）的HLA-DPB1会增加铍致敏风险，且并非慢性铍病所特有。该分子表面负电荷程度可能会增加慢性铍病风险，但不会增加致敏风险。在不存在Glu69的情况下，HLA-DRB1等位基因可能在铍呈递过程中发挥作用，增加慢性铍病风险。通过铍淋巴细胞增殖试验评估的T细胞反应依赖于中枢记忆T细胞，而导致肉芽肿性炎症和慢性铍病的Th1细胞因子分泌则依赖于效应记忆T细胞的活性。细胞因子基因多态性，如TGF-β1基因多态性，也会影响慢性铍病风险及病情严重程度。
目前铍致敏和慢性铍病的诊断标准依赖于铍淋巴细胞增殖试验。通过了解与铍致敏和慢性铍病相关的新免疫机制和遗传因素，我们或许能够提高利用新诊断方法检测铍对健康影响的能力，并有望改进疾病治疗方法。
