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 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 (THPA1236), cis-3,4,5,6-tetrahydrophthalic anhydride (THPA3456), cis-3-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA34), cis-4-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA44), phthalic anhydride (PA), 4-methylphthalic anhydride (MPA), and trimellitic anhydride (TMA) in olive oil. Specific IgE, IgG, IgG1, and IgG2 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 THPA3456 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 IgG1 and IgG2 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.
Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden.
H
H
Welinder
X
X
Zhang
C
C
Gustavsson
B
B
Björk
S
S
Skerfving
D000812:Anhydrides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D006241:Haptens / Q000378:metabolism; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007271:Injections, Intradermal; D008297:Male; D010323:Passive Cutaneous Anaphylaxis; D013329:Structure-Activity Relationship
D000812:Anhydrides; D000941:Antigens; D006241:Haptens; D007074:Immunoglobulin G; D007073:Immunoglobulin E