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 bery llium hypersensitivity. which can be measured in vitro by a lymphocyte prol iferation test. The objective of this study was to determine whether certai n allelic variations of the HLA-DPB1 gene, which had been observed previous ly in CBD, could be found in a group of individuals having beryllium hypers ensitivity, but no symptoms of CBD. A flow cytometry-based Lymphocyte Proli feration Test combined with immunophenotyping (Immuno-LPT) was used to dete ct CD4+ and CD8+ T cell proliferation in response to in vitro stimulation w ith beryllium. The HLA-DPB1 haplotypes of the same individuals were determi ned 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 si gnificantly high percentage (24%) were Glu69 homozygotes. Most of the CD4responders on the Immuno-LPT (10/14) carried rare, non-*0201 Glu69 DPB1 all eles: while most or the non-CD4+ responders (9/11) were common Glu69 carrie rs (*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 r esponse that Occurs in beryllium sensitization in the absence of clinical C BD. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.