Acute per-anesthetic hypersensitivity reaction (HSA-PA) is a rapidly occurring systemic reaction following injection of a drug during anesthesia (mortality between 3 and 9%). The substances responsible for these reactions in France are curare in 60% of cases, followed by antibiotics. The main mechanism mentioned is an immediate systemic hypersensitivity immune reaction mediated by IgE antibodies (anaphylaxis). NeuroMuscular Blocking Agents (NMBA; curare) relax skeletal muscles to facilitate surgeries and permit intubation, but lead to adverse reactions: (a) severe hypersensitivity reactions (anaphylaxis) thought to rely on pre-existing anti-NMBA antibodies; (b) complications due to postoperative residual curarization. Identification of patients at risk remains suboptimal due to the lack of adequate tools to detect anti-NMBA antibodies. A capturing agent exists for only one out of the four most used NMBAs, allowing reversal of profound curarization. Case reports suggested that it might also ameliorate an ongoing anaphylaxis due to that NMBA.
Based on strong preliminary results, our study proposes to characterize anti-drugs antibody repertoires in patients with various NMBA or antibiotics-anaphylaxis, describe activation pathways leading to anaphylaxis, develop and validate diagnostic and therapeutic molecules to ameliorate patient screening, NMBA-anaphylaxis and reverse profound neuromuscular block.
Age ≥ 18 years old and ≤ 70 years old
Patient having presented an allergic reaction in the operating room in the last 10 years, regardless of the grade of severity, the causative agent or the type of anesthesia
Patient having benefited from an allergy-anaesthesia consultation in the investigator center
Absence of written informed consent
Protected person: under guardianship or curatorship
Patient without social security
Pregnancy of breast feeding
Parallel
IgG group
Diagnostic testWill be performed : * a blood sampling of 5 ml (for realization of a basophil activation test) * a blood sampling of 250 ml
IgE group
Diagnostic testWill be performed : * a blood sampling of 5 ml (for realization of a basophil activation test) * a bone marrow sampling
IgG group + IgE group
Diagnostic test* a blood sampling of 5 ml (for realization of a basophil activation test) * a blood sampling of 250 ml * a bone marrow sampling
Obtain sequences of gene producers (VH and VL pairs) coding for the variable part of anti-drug antibodies, thanks to the isolation of B lymphocytes of antibodies directed against the responsible molecule, from blood cells or bone marrow
Production of recombinant antibodies based on obtained sequences
Purification system (AKTA 25L, Cytiva)
Evaluate antibodies properties, such as specificity
ELISA
Evaluate antibodies properties, such as avidity
Interferometry (Octet, ForteBio)
Ability of antibodies expressed as N297A mutated human IgG1 to reduce or block target curare-induced neuromuscular blockade without an immune response triggered by the antibody drug
Measure of muscle strength of mice
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
Institut Pasteur
Collaborator
