Issues in diisocyanate antibody testing

Diisocyanates are used to produce a wide variety of polyurethane products; they are also recognized as an important cause of occupational asthma. Their chemical reactivity presents challenges to toxicologists and clinicians alike seeking to understand the mechanisms underlying diisocyanate asthma. In this article, we review the literature on immunoassay detection of IgE and IgG binding to diisocyanate-protein conjugates and assess the utility of such testing as a diagnostic tool and exposure indicator. Data from 29 studies of occupational exposure to diisocyanates revealed considerable variability in assay methodology and heterogeneity in the prevalence of positive antibody responses across laboratories. In studies that included both confirmed diisocyanate asthma subjects and exposed nonasthmatics, positive IgE responses identified cases with low sensitivity (18-27%), but high specificity (96-98%). Detection of IgG binding to diisocyanate conjugates is an indirect, qualitative indicator of disease status and past diisocyanate exposure. The utility of these assays is limited, however, due to a lack of (1) method standardization, (2) population norms to guide interpretation of results, and (3) demonstration that the assays improve either on disease prediction or on exposure confirmation beyond that of other indicators. Sources of assay heterogeneity are discussed and suggestions are offered for improving test performance and interpretability.