Beryllium sensitivity is linked to HLA-DP genotype.
Chronic beryllium disease (CBD) appears to arise from a combination of both exposure and genetic risk factors. A distinguishing feature of CBD is beryllium hypersensitivity, which can be measured in vitro by a lymphocyte proliferation test. The objective of this study was to determine whether certain allelic variations of the HLA-DPB1 gene, which had been observed previously in CBD, could be found in a group of individuals having beryllium hypersensitivity, but no symptoms of CBD. A flow cytometry-based Lymphocyte Proliferation Test combined with immunophenotyping (Immuno-LPT) was used to detect CD4+ and CD8+ T cell proliferation in response to in vitro stimulation with beryllium. The HLA-DPB1 haplotypes of the same individuals were determined by automated DNA sequencing. Twenty-two out of 25 beryllium-sensitive, non-CBD individuals were found to be carriers of the HLA-DPB1 gene having a substitution of a glutamic acid at position 69 in Exon 2 (Glu69), and a significantly high percentage (24%) were Glu69 homozygotes. Most of the CD4+ responders on the Immuno-LPT (10/14) carried rare, non-*0201 Glu69 DPB1 alleles; while most of the non-CD4+ responders (9/11) were common Glu69 carriers (*0201 or *0202) or non-Glu69 individuals (non-Glu69/non-Glu69). This is the first direct evidence that HLA-DP genotype is linked to a phenotypic response that occurs in beryllium sensitization in the absence of clinical CBD.
Wang
Z
Z
B-2, M888, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Farris
G M
GM
Newman
L S
LS
Shou
Y
Y
Maier
L A
LA
Smith
H N
HN
Marrone
B L
BL
D001607:Berylliosis / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D002908:Chronic Disease; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D010641:Phenotype; D011237:Predictive Value of Tests; D016176:T-Lymphocyte Subsets
D006682:HLA-DP Antigens; D004247:DNA