title: Cross-reactivity of anti-phosphorylcholine antibodies to neuromuscular blockers in a murine model of immunization.
abstract: Hypersensitivity reactions to curare-like neuromuscular blocking agents (NMBA) used in anesthesiology are more frequent in females and often occur at the first exposure to these drugs. To evaluate the antibody response to a hapten sharing the same allergenic epitope with NMBA in a murine model of immunization with Nitrophenylphosphorylcholine (NPPC) coupled with Keyhole Limpet Hemocyanin (KLH). BALB/c mice from both sexes were intraperitoneally immunized with NPPC-KLH with alum and boosted twice, on 7 and 14 days. The antibodies were tested for specificity to PC and for cross-reactivity to the haptens, NPPC and PC, as well as to the NMBAs. Mice immunized with NPPC-KLH produced anti-PC antibodies mainly of IgM, IgG1 and IgG3 isotypes, at similar levels in both sexes. Different affinities for the haptens were detectable between isotypes, with anti-PC IgG3 antibody reactivity mostly related to the choline portion of the NPPC hapten. When comparing among sexes, females developed greater IgG2 affinity to the hapten than males. Cross-reactivity to NMBAs was predominant among the anti-PC IgG3 antibodies, mainly in females achieving 75% of inhibition with 16 mM of suxamethonium, while other isotypes achieved up to 30% and was absent for IgE. The investigation of antibody isotypes regarding sensitization to choline-derived structures could contribute to understanding the differential ability of females to produce antibodies that are cross-reactive with NMBAs.
authors.affiliation: Laboratory of Investigation in Dermatology and Immunodeficiencies, LIM-56, School of Medicine, University of São Paulo, Brazil.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Mazzuco
authors.forename: Maria Notomi
authors.initials: MN
authors.lastname: Sato
authors.forename: Dewton de Moraes
authors.initials: Dde M
authors.lastname: Vasconcelos
authors.forename: Alberto José da Silva
authors.initials: AJ
authors.lastname: Duarte
mesh_terms: D000818:Animals; D000906:Antibodies / Q000502:physiology*; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007114:Immunization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009466:Neuromuscular Blocking Agents / Q000276:immunology*; D010767:Phosphorylcholine / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000906:Antibodies; D009466:Neuromuscular Blocking Agents; D010767:Phosphorylcholine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin