Role of human leukocyte antigen phenotype and exposure in development of occupational asthma.

Studies of factory workforces in the past decade, exposed to both inhaled protein allergens (e.g. enzymes) and low molecular weight sensitisers (e.g. acid anhydrides), have provided consistent evidence of exposure-response relationships for both sensitisation (IgE production) and asthma. The development of molecular techniques has allowed investigation of candidate gene, in particular HLA Class 2 alleles, as risk factors contributing to individual susceptibility, in particular to low molecular weight chemicals. The frequency of HLA DR3 in cases of sensitisation to trimellitic anhydride and ammonium hexachloroplatinate is increased as compared to referents who have experienced a comparable intensity and duration of exposure. Similarly, HLA DQB1Asp57 is consistently more frequent in cases of isocyanate induced asthma. These observations indicate HLA Class 2 molecules contribute to individual susceptibility to sensitisation and asthma caused by low molecular weight chemicals. A study of platinum refinery workers suggested the relative risk associated with HLA phenotype was greater at lower levels of exposure.