Influence of MHC CLASS II in Susceptibility to Beryllium Sensitization and Chronic Beryllium Disease
| Autor: | Lori J. Silveira, Hiroe Sato, Andrew P. Fontenot, P. A. Lympany, Lisa A. Maier, Richard T. Sawyer, Eric Wilcox, Roland M. du Bois, Ken Welsh, Dierdre S. McGrath, Lee S. Newman |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male HLA-DP Antigens Vital capacity Genotype Berylliosis Immunology Glutamic Acid Severity of Illness Index digestive system Pulmonary function testing Epitopes HLA Antigens HLA-DQ Antigens medicine HLA-DQ beta-Chains Humans Immunology and Allergy Genetic Predisposition to Disease Allele HLA-DP beta-Chains Sensitization Aged Polymorphism Genetic business.industry Histocompatibility Antigens Class II HLA-DR Antigens Odds ratio Middle Aged medicine.disease digestive system diseases HLA-DRB5 Chains surgical procedures operative medicine.anatomical_structure Case-Control Studies Chronic Disease Female Immunization Beryllium HLA-DRB3 Chains business HLA-DRB4 Chains HLA-DRB1 Chains Beryllium Disease |
| Zdroj: | The Journal of Immunology. 171:6910-6918 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.171.12.6910 |
| Popis: | A glutamic acid at residue 69(Glu69) in the HLA-DPB1 gene (Glu69) is associated with chronic beryllium disease (CBD) and possibly beryllium sensitization (BeS). This study tested the hypothesis that MHC class II polymorphisms are important in susceptibility to BeS and CBD and that the Glu69 variant is related to markers of disease severity. Genomic DNA was obtained from BeS (n = 50), CBD (n = 104), and beryllium-exposed nondiseased (Be-nondiseased) (n = 125) subjects. HLA-DPB1, -DRB1, and -DQB1 genotypes were determined by (sequence-specific primers) PCR. Disease severity was assessed by pulmonary function and exercise testing. A higher frequency of the DPB1 Glu69 gene was found in CBD and BeS compared with the Be-nondiseased subjects, with odds ratios of 10.1 for CBD vs Be-nondiseased and 9.5 for BeS vs Be-nondiseased. The majority of BeS and CBD subjects displayed non-0201 Glu69 alleles. Glu69 homozygosity was higher in the CBD subjects, while BeS subjects were intermediate and Be-nondiseased lowest. DRB1*01 and DQB1*05 phenotypes were reduced in CBD vs Be-nondiseased subjects, while DRB1*13 and DQB1*06 were associated with CBD in the absence of Glu69. Markers of disease severity, including a lower forced vital capacity, diffusion capacity for carbon monoxide, PaO2 at rest, maximum workload on exercise testing, and a higher arterial-alveolar gradient at rest, were associated with Glu69 homozygosity. We conclude that DPB1 Glu69 is a marker of sensitization and not specific for disease. Glu69 homozygosity acts as a functional marker associated with markers of CBD severity. |
| Databáze: | OpenAIRE |
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