Repertoire and Properties of Anti-drug Antibodies Involved in Immediate Hypersensitivity in the Operating Room

Condition(s) studied

Investigational drug(s) / intervention(s)

IgG group: Will be performed : * a blood sampling of 5 ml (for realization of a basophil activation test) * a blood sampling of 250 ml

IgE group: Will be performed : * a blood sampling of 5 ml (for realization of a basophil activation test) * a bone marrow sampling

IgG group + IgE group: * a blood sampling of 5 ml (for realization of a basophil activation test) * a blood sampling of 250 ml * a bone marrow sampling

Study summary

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.

Eligibility

Primary outcome measure(s)

• 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 — up to 10 years

Trial sites (1)

More Assistance Publique - Hôpitaux de Paris trials in France