Use of structural alterations in the synthesis of halothane metabolite antigens to mimic halothane-induced immunogen

Andrea K. Hubbard, John P. Levy, Timothy P. Roth, A Jay Gandolfi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Four hapten-carrier conjugates were synthesized to evaluate any potential antigenic similarities between these synthetic compounds and the immunogens induced in vivo by the anesthetic, halothane and, thus, be used eventually as a more sensitive probe to detect the presence of these halothane-induced antibodies in halothane-exposed individuals. In this study, antibodies from five halothane hepatitis patients were used to evaluate these antigenic alterations since the specificity of these antibodies would most accurately reflect the antigenic structure of halothane-induced immunogens. Quantitation of antibody binding to these synthetic proteins was determined in an enzyme linked immunosorbent assay and immunoblot techniques. Trifluoroacetylated rabbit serum albumin was 5 times more reactive with these antibodies and thus more antigenic than the homologous acetylated moiety confirming the importance of the trifluoromethyl moiety as an epitope in the immunogen in vivo. Insertion of a spacer arm, aminocaproic acid, between the hapten and carrier moieties and an epitope density of 40% acetylation also increased antigenicity. Through these structural alterations produced in vitro, antigenic compounds have been produced which may resemble more closely the immunogen elicited in vivo and which may ultimately serve as more sensitive probes for halothane-induced antibodies from exposed individuals.

Original languageEnglish (US)
Pages (from-to)93-112
Number of pages20
JournalDrug and Chemical Toxicology
Volume13
Issue number2-3
DOIs
StatePublished - 1990

Fingerprint

Halothane
Antigens
Metabolites
Antibodies
Haptens
Epitopes
Aminocaproic Acid
Synthetic Vaccines
Antibody Specificity
Acetylation
Anesthetics
Immunosorbents
Serum Albumin
Enzyme-Linked Immunosorbent Assay
Assays
Rabbits
Enzymes
Proteins
Acids

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health
  • Chemical Health and Safety
  • Chemistry(all)

Cite this

Use of structural alterations in the synthesis of halothane metabolite antigens to mimic halothane-induced immunogen. / Hubbard, Andrea K.; Levy, John P.; Roth, Timothy P.; Gandolfi, A Jay.

In: Drug and Chemical Toxicology, Vol. 13, No. 2-3, 1990, p. 93-112.

Research output: Contribution to journalArticle

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