title: Antibody specificity to the chemical structures of organic acid anhydrides studied by in-vitro and in-vivo methods.
abstract: 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.
authors.affiliation: Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden.
authors.forename: X D
authors.initials: XD
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Lötvall
authors.forename: S
authors.initials: S
authors.lastname: Skerfving
authors.forename: H
authors.initials: H
authors.lastname: Welinder
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000812:Anhydrides / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D000918:Antibody Specificity / Q000187:drug effects* / Q000276:immunology; D000937:Antigen-Antibody Reactions; D001985:Bronchial Provocation Tests; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006168:Guinea Pigs; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D010323:Passive Cutaneous Anaphylaxis; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000812:Anhydrides; D007074:Immunoglobulin G