BACKGROUND: Toluene diisocyanate (TDI), a widely used aromatic diisocyanate with the potential to cause asthma, reacts with albumin in the airway fluid, which acts as a carrier protein for chemical presentation to the immune system. Structural elucidation of TDI-albumin conjugates is crucial to understanding the human immune response to TDI exposure.
OBJECTIVE: Investigate the dependence of TDI's antigenicity on the biophysics of exposure and its association with TDI asthma.
METHODS: Toluene diisocyanate-albumin conjugates were generated by exposing albumin to TDI in liquid or vapor phase (liquid or vapor TDI-albumin, respectively). Conjugates were characterized by native gel electrophoresis and matrix-assisted laser desorption/ionization-mass spectrometry, and used as antigens in ELISA assays for serum specific-IgE and IgG.
RESULTS: The physical phase of TDI (vapor vs liquid) affects the formation of TDI-albumin conjugates, with measurable differences in the amount of TDI per albumin molecule, migration in native gels, matrix-assisted laser desorption/ionization-mass spectrometry mass/charge spectra, and antigenicity. Vapor TDI-albumin conjugates were recognized by IgE from 44% of subjects with TDI asthma, whereas liquid TDI-albumin conjugates are recognized by IgE from only 17% of these patients. A significant (P < .05) association between TDI exposure and vapor TDI-albumin specific serum IgG was also observed.
CONCLUSION: Biophysics of TDI exposure substantially affects formation of TDI-albumin conjugates recognized by the immune system in association with exposure and asthma.
CLINICAL IMPLICATIONS: The data suggest that serology may help identify TDI asthmatics and exposed workers if the appropriate form of TDI is used as the antigenic basis for analysis.
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