Am. J. Respir. Crit. Care Med.,
Volume 156, Number 4, October 1997, S139-S143
Human Leukocyte Antigen Associations in
Occupational Asthma Induced by Isocyanates
C. E.
MAPP,
A.
BALBONI,
R.
BARICORDI,
and
L. M.
FABBRI
Institute of Occupational Medicine, University of Padova; Institute of Human Genetics and Institute of Infectious and
Respiratory Diseases, University of Ferrara, Italy
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. Mapp CE, Balboni A, Baricordi R, Fabbri LM. Human leukocyte antigen associations in occupational asthma induced by isocyanates.
