title: Differentiating the cellular and humoral components of neuromuscular blocking agent-induced anaphylactic reactions in patients undergoing anaesthesia.
abstract: BACKGROUND
  The significance of IgE antibodies to neuromuscular blocking agent (NMBA)-induced anaphylactic reactions during anaesthesia is unclear. We investigated the relevance of IgE to rocuronium using an in vitro technique.
  
  
  METHODS
  Serum samples from 61 patients with anaphylactic reactions during anaesthesia were investigated. On the basis of clinical history, allergy to NMBA was considered likely in 48 patients, further assessed using intradermal skin tests for several commonly used NMBAs, including rocuronium, vecuronium, and succinylcholine. To determine the presence of rocuronium IgE in human serum, a rocuronium-human serum albumin (rocHSA) conjugate was coupled to a solid phase and a radioallergosorbent test performed. The biological effects of patient serum NMBA-IgE on histamine release were investigated using in vitro sensitized basophils from healthy blood donors.
  
  
  RESULTS
  IgE to rocuronium was found in 23 of 48 serum samples (48%) with NMBA allergy, although only two of these were able to sensitize basophils to release histamine in response to rocHSA. IgE-responsiveness in the basophil test was only observed with conjugated rocHSA and not with unconjugated rocuronium or the other NMBAs evaluated. However, unconjugated rocuronium inhibited the histamine release induced by rocHSA. Correlation between skin-test reactivity to rocuronium and IgE to rocHSA was low (P>0.1). In contrast, striking correlation between IgE to rocuronium and skin-test reactivity to succinylcholine was found (P<0.001).
  
  
  CONCLUSIONS
  Our results indicate that NMBA-related anaphylaxis requires not only IgE NMBA reactivity, but also altered cellular reactivity in the patient. The latter may be demonstrable by testing basophils from the patient, a skin test with (steroidal) NMBA, or both.
authors.affiliation: Department of Immunopathology, Sanquin Research, Plesmanlaan 125, 1066CX Amsterdam, The Netherlands. r.aalberse@sanquin.nl
authors.forename: R C
authors.initials: RC
authors.lastname: Aalberse
authors.forename: I
authors.initials: I
authors.lastname: Kleine Budde
authors.forename: M
authors.initials: M
authors.lastname: Mulder
authors.forename: S O
authors.initials: SO
authors.lastname: Stapel
authors.forename: W
authors.initials: W
authors.lastname: Paulij
authors.forename: F
authors.initials: F
authors.lastname: Leynadier
authors.forename: M W
authors.initials: MW
authors.lastname: Hollmann
mesh_terms: D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000139:chemically induced* / Q000276:immunology; D000732:Androstanols / Q000009:adverse effects / Q000276:immunology*; D000768:Anesthesia, General; D000918:Antibody Specificity; D015549:Basophil Degranulation Test / Q000379:methods; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007431:Intraoperative Complications / Q000139:chemically induced* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D003473:Neuromuscular Nondepolarizing Agents / Q000009:adverse effects / Q000276:immunology*; D011852:Radioallergosorbent Test / Q000379:methods; D000077123:Rocuronium; D012882:Skin Tests / Q000379:methods
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D007073:Immunoglobulin E; D000077123:Rocuronium