Antibody specificity to the chemical structures of organic acid anhydrides studied by in-vitro and in-vivo methods.

The objective of the study was to evaluate the structure-activity relationship for the antigenic activity of different organic acid anhydrides (OAAs). The specificity of guinea pig (GP) IgG1 to different anhydrides was studied by ELISA-inhibition, PCA, and airway provocation tests of cross-reactivity with different OAA conjugates. In the airway provocation tests, lung resistance and plasma extravasation of Evan's Blue dye was measured. The ELISA-inhibition tests showed a wide range in antibody specificity. Modelling of ring configuration, methyl group substitution, double bond position, and cis/trans isomerism of anhydride forming carboxyl groups influenced the specificity. There was a general consistency in cross-reactivity of anti-cis-hexahydrophthalic anhydride IgG1 versus GP serum albumin conjugates of trans-hexahydrophthalic anhydride, phthalic anhydride, and succinic anhydride as shown by ELISA-inhibition, PCA, and airway provocation tests. It is concluded that various modifications of the chemical structures of a hapten are recognized by the hapten-specific antibodies, and that these differences may have clinical relevance. In particular, the ring structure and the positions of double bonds and of methyl groups are important. Further, the in-vitro ELISA-inhibition tests show a good agreement with the in-vivo PCA and bronchial provocation tests.