title: Human leukocyte antigen associations in occupational asthma induced by isocyanates.
abstract: Exposure to diisocyanates is recognized as a leading cause of occupational asthma. Occupational asthma induced by isocyanates shares many characteristics with immunoglobulin E (IgE)-mediated asthma: in both, the responsible agent is known, and the clinical presentation, response to inhalation challenge in the laboratory, and response to antiasthma drugs are similar. Although asthma mediated by an IgE mechanism occurs in atopic subjects, occupational asthma induced by isocyanates occurs mostly in nonatopic asthmatics, and an IgE-mediated mechanism has not been consistently demonstrated. However, activated T lymphocytes, methacromatic cells, and eosinophils are increased in the bronchial mucosa of allergic and nonallergic asthmatics and subjects with occupational asthma induced by isocyanates, suggesting similar, probably immunologically mediated mechanisms for both nonoccupational and occupational asthma. Occupational asthma occurs in up to 5-10% of the exposed subjects. Evaluation of major histocompatibility complex (MHC) class II genes in exposed subjects who develop toluene diisocyanate (TDI) asthma has shown a negative association with HLA-DQB1*0501 and a positive association with HLA-DQB1*0503 alleles. In addition, a high proportion of TDI asthmatics express the HLA-DQB1*0503-associated aspartic acid at residue 57, suggesting that HLA-DQ may have a key role in conferring susceptibility. Thus, asthma induced by the low-molecular-weight agent TDI may result from an immunologic reaction due to the interaction of genetic susceptibility with exposure in the workplace.
authors.affiliation: Institute of Occupational Medicine, University of Padova, Italy.
authors.forename: C E
authors.initials: CE
authors.lastname: Mapp
authors.forename: A
authors.initials: A
authors.lastname: Balboni
authors.forename: R
authors.initials: R
authors.lastname: Baricordi
authors.forename: L M
authors.initials: LM
authors.lastname: Fabbri
mesh_terms: D000906:Antibodies / Q000276:immunology; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D017953:Isocyanates / Q000009:adverse effects*; D009784:Occupational Diseases / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D000949:Histocompatibility Antigens Class II; D017953:Isocyanates; D007073:Immunoglobulin E