Structure-activity relationships of organic acid anhydrides as antigens in an animal model

Abstract

Relationships between chemical structure and immunogenicity have been studied in 13 dicarboxylic acid anhydrides. Guinea-pigs were immunized intradermally by a single dose of 0.3 M solutions of succinic anhydride (SA), maleic anhydride (MA), methylmaleic anhydride (MMA), cis-cyclohexane-1,2-dicarboxylic anhydride ( cis-HHPA), trans-cyclohexane-1, 2-dicarboxylic anhydride ( trans-HHPA), 4-methylcyclohexane-1,2-dicarboxylic anhydride (MHHPA), cis-1,2,3,6-tetrahydrophthalic anhydride (THPA 1236), cis-3,4,5,6-tetrahydrophthalic anhydride (THPA 3456), cis-3-methylcyclohex-4-ene-1, 2-dicarboxylic anhydride (MTHPA 34), cis-4-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA 44), phthalic anhydride (PA), 4-methylphthalic anhydride (MPA), and trimellitic anhydride (TMA) in olive oil. Specific IgE, IgG, IgG 1, and IgG 2 antibodies against guinea-pig serum albumin conjugates of the anhydrides were determined by passive cutaneous anaphylaxis (PCA) tests and enzyme-linked immunoabsorbant assay (ELISA). Specific IgG was significantly increased in all animals, except those immunized with THPA 3456 and SA, which sensitized only 3 9 and 7 9 animals, respectively. Furthermore, the specific IgG values were very low in the SA group. The titers of specific IgG, and IgG 2 were increased in the IgG-positive animals. Specific IgE was positive in all animals immunized with MA, MHHPA, MTHPA (both isomers), and MPA, and in 6 9 and 5 9 guinea pigs immunized with TMA and MMA, respectively. The IgE titers were generally very low; PCA was negative after dilutions to 1:32, or less. The results indicate a considerable variation in the sensitizing potential between different organic acid anhydrides. The most marked general effect of the chemical structure on immunogenicity was the enhancement of antibody formation when a hydrogen atom in the anhydride was substituted with a methyl group.