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Am. J. Respir. Crit. Care Med., Volume 165, Number 6, March 2002, 788-794

Human Leukocyte Antigen Class II Amino Acid Epitopes
Susceptibility and Progression Markers for Beryllium Hypersensitivity

MILTON D. ROSSMAN, JOSE STUBBS, CHUNG WHA LEE, ELIAS ARGYRIS, ELENI MAGIRA, and DIMITRI MONOS

Departments of Medicine and Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and Laboratory of Human Biology and Genetics, Democritus University of Thrace, School of Medicine, Alexandroupolis, Greece

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 (pcorr < 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.




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