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 rela tionship for the antigenic activity of different organic acid anhydrid es (OAAs). The specificity of guinea pig (GP) IgG(1) to different anhy drides was studied by ELISA-inhibition, PCA, and airway provocation te sts of cross-reactivity with different OAA conjugates. In the airway p rovocation tests, lung resistance and plasma extravasation of Evan's B lue dye was measured. The ELISA-inhibition tests showed a wide range i n antibody specificity. Modelling of ring configuration, methyl group substitution, double bond position, and cis/trans isomerism of anhydri de forming carboxyl groups influenced the specificity. There was a gen eral consistency in cross-reactivity of anti-cis-hexahydrophthalic anh ydride IgG(1) versus GP serum albumin conjugates of trans-hexahydropht halic anhydride, phthalic anhydride, and succinic anhydride as shown b y 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 differen ces may have clinical relevance. In particular, the ring structure and the positions of double bonds and of methyl groups are important. Fur ther, the in-vitro ELISA-inhibition tests show a good agreement with t he in-vivo PCA and bronchial provocation tests. (C) 1997 Elsevier Scie nce Ireland Ltd.