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

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.

Conditions

• Hypersensitivity, Immediate
• Peri-operative Injury
• Antibiotic Allergy
• Antibody Hypersensitivity

Interventions

DIAGNOSTIC_TEST

IgG group

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

DIAGNOSTIC_TEST

IgE group

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

DIAGNOSTIC_TEST

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

Sponsors & Collaborators

• Institut Pasteur

  collaborator INDUSTRY

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Aurelie Gouel, MD, PhD · Assistance Publique - Hôpitaux de Paris

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-04-12

Primary Completion

2033-04-12

Completion

2033-12-15

Countries

• France

Study Locations