Immunology of chronic beryllium disease.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Samuel
George
G
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.
Maier
Lisa A
LA
D001607:Berylliosis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology
D016207:Cytokines; D006681:HLA-D Antigens