Cross-reactivity of anti-phosphorylcholine antibodies to neuromuscular blockers in a murine model of immunization.
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.
Mazzuco
Rosa Maria
RM
Laboratory of Investigation in Dermatology and Immunodeficiencies, LIM-56, School of Medicine, University of São Paulo, Brazil.
Sato
Maria Notomi
MN
Vasconcelos
Dewton de Moraes
Dde M
Duarte
Alberto José da Silva
AJ
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
D000906:Antibodies; D009466:Neuromuscular Blocking Agents; D010767:Phosphorylcholine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin