title: Interaction of HLA phenotype and exposure intensity in sensitization to complex platinum salts.
abstract: The development of sensitization to inhaled allergens is determined by the interaction of multiple genetic and environmental influences. Occupational sensitization to low-molecular-weight chemicals allows a specific immunological response to an inhaled hapten to be studied in a well-defined population with characterized exposure. We investigated the workforce of a large platinum refinery exposed to ammonium hexachloroplatinate (ACP) to test the hypothesis that the development of IgE-associated sensitization to ACP was influenced by human leukocyte-associated antigen (HLA) phenotype, especially in those with lower ACP exposure. We performed HLA typing in 44 cases with a positive skin prick test to ACP, and 57 nonsensitized referents matched on age, race, duration of employment, and category of ACP exposure. An HLA-DR3 phenotype was more common among cases (odds ratio [OR] 2.3), and more so in those with low (OR infinite) than with high exposure (OR 1.6); HLA-DR6 was less common among the cases (OR 0.4), an association also stronger in the low-exposure group (OR 0.1 versus 0.5). These results provide evidence that HLA phenotype is a significant determinant of sensitization to complex platinum salts and for the first time show that the strength of this association varies with intensity of exposure to the sensitizing agent. They imply that as exposure-control measures are taken to prevent occupational sensitization and, by analogy, sensitization to allergens outside the workplace, disease incidence will increasingly be determined by genetic susceptibility.
authors.affiliation: Department of Occupational and Environmental Medicine, Imperial College School of Medicine (National Heart and Lung Institute), London, United Kingdom.
authors.forename: A J
authors.initials: AJ
authors.lastname: Newman Taylor
authors.forename: P
authors.initials: P
authors.lastname: Cullinan
authors.forename: P A
authors.initials: PA
authors.lastname: Lympany
authors.forename: J M
authors.initials: JM
authors.lastname: Harris
authors.forename: R J
authors.initials: RJ
authors.lastname: Dowdeswell
authors.forename: R M
authors.initials: RM
authors.lastname: du Bois
mesh_terms: D000328:Adult; D002712:Chlorides / Q000009:adverse effects / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics; D015808:HLA-DR6 Antigen / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007428:Intradermal Tests; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000235:genetics* / Q000276:immunology; D016017:Odds Ratio; D010641:Phenotype; D017671:Platinum Compounds / Q000009:adverse effects* / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors
chemical_list: D002712:Chlorides; D006680:HLA Antigens; D015803:HLA-DR3 Antigen; D015808:HLA-DR6 Antigen; D017671:Platinum Compounds; C018453:ammonium hexachloroplatinate; D007073:Immunoglobulin E