Role of Neutrophil Activation in Anaphylaxis to Curare (NASA)
In about 10% of preoperative anaphylactic reactions to curare (114 patients analyzed at the BICHAT Hospital), a classical mechanism (mast cell- and IgE-dependent) is not identified. The mechanisms underlying these atypical anaphylactic reactions are unknown. The investigators have developed at the Pasteur Institute a murine model of anaphylaxis in which neutrophils, IgG and Platelet Activating Factor (PAF) play predominant roles. In addition, preliminary results obtained at the BICHAT Hospital suggest the presence of specific IgG anti-quaternary ammonium in the sera of patients that had developed a shock to curare anesthesia, but not in controls exposed to curare anesthesia or in normal blood donors. Finally, the release of neutrophil extracellular traps (NETs), extracellular filaments made of DNA and histones, may contribute to respiratory symptoms.
HYPOTHESIS: Neutrophils are implicated in curare-induced anaphylactic reactions in humans. Activated by IgG-curare complexes, which aggregate IgG receptors, neutrophils release PAF and NETs that are implicated in the cardiac and respiratory distress during anaphylaxis. It is possible that the activation of neutrophils: 1) explains the clinical features of atypical anaphylactic reactions (non-IgE mediated), 2) participates also in part to classical anaphylactic reactions
GENERAL OBJECTIVE: Compare the percentage of circulating activated neutrophils in a group of patients immediately following a curare-induced shock (case) to that of a group of patients exposed to curare during anesthesia without developing a shock (control).
SECONDARY OBJECTIVES: A) the day of the shock, quantify and compare between case and controls, 1) the level of circulating anti-quaternary ammonium IgG by immuno fluorometry, 2) the expression of IgG receptors (FcR) on the surface of neutrophils by cytometry, 3) the levels of circulating PAF by mass spectrometry, 4) the amount of NETs by immunofluorescence.
B) 6 to 10 weeks after the shock perform, 1) cutaneous tests to curare, 2) a study of the capacity of stimulation of ex vivo neutrophils by IgG-curare complexes
|Anaphylactic Shock to Curare||Biological: Blood volume collected specifically for this study|
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Role of Neutrophil Activation in Anaphylaxis to Curare|
- Percentage of circulating activated neutrophils in the group case compared to that of the group of control. [ Time Frame: 30min post-anaphylactic shock ]This measure will be based on the intensity of expression of the activation marker CD62L (L-selectin) by blood neutrophils using flow cytometry. Our preliminary data indicate that the Mean Fluorescence Intensity (MFI) of CD62L is >450 when considering " non-activated " neutrophils, and CD62L(MFI)<300 when considering " activated " neutrophils.
- the group case compared to the group of control. [ Time Frame: 30min post-anaphylactic shock ]Levels of anti-quaternary ammonium specific IgG in the plasma of "cases" than in the plasma of "controls"
- the group case compared to the group of control. [ Time Frame: 30min post-anaphylactic shock ]Ex vivo activation capacity of blood neutrophils in the presence of neuromuscular blocking drug-IgG immune complexes
- the group case compared to the group of control. [ Time Frame: 30min post-anaphylactic shock ]Presence of Neutrophil Extracellular Traps in the bronchial aspiration fluid of "cases"
|Study Start Date:||August 2012|
|Study Completion Date:||December 2015|
|Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Blood volume collected specifically for this study
Biological: Blood volume collected specifically for this study
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01637220
|Paris, France, 75018|
|Principal Investigator:||Sylvie Chollet-Martin, MD-PhD||Assistance Publique - Hôpitaux de Paris|