ベリリウム肺

慢性アレルギー疾患を起こすベリリウム暴露が、HLAクラスII　DPB1の多型と関連があるという話をラジオで聞きましたので、ご紹介します。

 

 

ベリリウム肺(症) (Berylliosis) または慢性ベリリウム症 (chronic beryllium disease, CBD) はベリリウムおよびベリリウム化合物への曝露によって肺に生ずる慢性アレルギー性疾患であり、ベリリウム中毒（英語版）の一症状である。航空宇宙産業やベリリウム鉱山、蛍光灯工場（かつて蛍光体にベリリウム化合物が用いられていたため）の作業者に職業病として多発した^[1][2]。

英語のウィキ

Several studies have shown that there is a genetic component to beryllium sensitivity. Specifically, those beryllium exposed workers with a mutation at the HLA-DPB1 Glu⁶⁹ position have increased prevalence of beryllium sensitization and CBD.

 

 

 

HLA class II DPB1 and DRB1 polymorphisms associated with genetic susceptibility to beryllium toxicity

 

Abstract

Objectives Chronic beryllium disease (CBD) is a hypersensitivity granulomatous pulmonary disease caused by exposure to the metal beryllium (Be²⁺). Our objective was to extend current knowledge of the genetics of beryllium disease by examining all HLA-DPB1 and HLA-DPR1 gene polymorphisms and the interactions between them.

Methods DNA-based typing of HLA-DPB1 and HLA-DRB1 loci at the allele level was performed on 65 CBD, 44 beryllium sensitised (BeS) but without CBD and 288 non-affected, beryllium exposed controls.

Results The DPβE69 residue regardless of zygosity, but particularly if present on non-*0201 alleles, was of primary importance for the development of CBD and BeS, while other negatively charged residues DPβDE55, 56 and DPβDE84, 85 incrementally increased, although not independently, the risk. The DPβE69 positive alleles with charge −7 or −9 were associated with both CBD and BeS. The polymorphic residues DPβE69, DPβDE55, 56 and DPβDE84, 85 were responsible for the −9 charge and the first two residues for the −7 charge.

Conclusions In the absence of DPβE69, DRβE71 is a risk factor for CBD and BeS. DPβE69 and DRβE71 are adjacent to other amino acids that are also negatively charged, suggesting that the positively charged Be²⁺ modifies the local environment of the epitopes in a way that promotes interactions between peptides and T cells and results in CBD. Finally, the protective effect of the DPB1*0201 positive haplotype may involve particular polymorphisms outside of the DPB1 gene.