STRUCTURE-ACTIVITY-RELATIONSHIPS OF ORGANIC-ACID ANHYDRIDES AS ANTIGENS IN AN ANIMAL-MODEL

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 anhydri de (SA), maleic anhydride (MA), methylmaleic anhydride (MMA), cis-cycl ohexane-1,2-dicarboxylic anhydride (cis-HHPA), trans-cyclohexane-1, 2- dicarboxylic anhydride (trans-HHPA), 4-methylcyclohexane-1,2-dicarboxy lic anhydride (MHHPA), cis-1,2,3,6-tetrahydrophthalic anhydride (THPA( 1236)), cis-3,4,5,6-tetrahydrophthalic anhydride (THPA(3456)), cis-3-m ethylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA(44)), cis-4-meth ylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA,), phthalic anhydri de (PA), 4-methylphthalic anhydride (MPA), and trimellitic anhydride ( TMA) in olive oil. Specific IgE, IgG, IgG(1), and IgG, antibodies agai nst guinea-pig serum albumin conjugates of the anhydrides were determi ned by passive cutaneous anaphylaxis (PCA) tests and enzyme-linked imm unoabsorbant assay (ELISA). Specific IgG was significantly increased i n all animals, except those immunized with THPA,,,, and SA, which sens itized only 3/9 and 7/9 animals, respectively. Furthermore, the specif ic IgG values were very low in the SA group. The titers of specific Ig G, and IgG(2) were increased in the IgG-positive animals. Specific IgE was positive in all animals immunized with MA, MHHPA, MTHPA (both iso mers), 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 neg ative after dilutions to 1:32, or less. The results indicate a conside rable variation in the sensitizing potential between different organic acid anhydrides. The most marked general effect of the chemical struc ture on immunogenicity was the enhancement of antibody formation when a hydrogen atom in the anhydride was substituted with a methyl group.