Pierre Bruhns - Clinical and pathological consequences of human anti-drug antibodies (NASA study) - Research

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Clinical and pathological consequences of human anti-drug antibodies (NASA study) that aims at demonstrating in the clinic that neutrophils are activated by antibody-curare complexes and involved in curare-induced anaphylaxis (allergic shock) in humans, and at establishing in parallel a mouse model of curare-induced anaphylaxis.

http://clinicaltrials.gov/ct2/show/NCT01637220

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

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Clinical and pathological consequences of human anti-drug antibodies (NASA study)

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