Diisocyanate antigens that detect specific antibodies in exposed workers and guinea pigs

Evaluation of the immunologic contribution to the pathogenesis of isocyanate lung disease necessitates preparation of isocyanate-protein conjugates to detect anti-isocyanate antibodies. The preparation and characterization of the conjugates were described in the preceding paper in this issue. Sera were obtained from two guinea pigs immunized with 4,4'-diisocyanatodiphenylmethane (MDI) and from three workers with occupational exposure to MDI. By use of Western blot analysis, guinea pig IgG antibodies were best detected by the monomeric component of MDI-guinea pig serum albumin. ELISA additionally indicated that conjugates which contained a high density of hapten detected greater amounts of antibody than did conjugates containing low amounts of hapten. The same procedures were then used to assess the amount of MDI-specific IgG and IgE antibody in sera from symptomatic workers. Effective MDI-HSA antigens were those that were monomeric and had high haptenic content. Highly substituted conjugates of monoisocyanates (phenyl isocyanate and p-tolyl isocyanate) with serum albumins were also effective in detecting antibodies to MDI. These results indicate the importance of the composition of isocyanate conjugate antigens in detecting antibodies to diisocyanates and suggest that standards be developed for preparation and characterization of these diagnostic serologic reagents.