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

NCT05420935 | Recruiting

• 1 other identifier: APHP211277
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Hypersensitivity, IgE, IgG, repertoire, NMBA, anaphylaxis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• Production of recombinant antibodies based on obtained sequences

  up to 10 years

• Evaluate antibodies properties, such as specificity

  up to 10 years

• Evaluate antibodies properties, such as avidity

  up to 10 years

• 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

  up to 10 years

• 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

  up to 10 years

Study Arms (3)

IgG group

OTHER

Patient in the IgG group will benefit from a blood sampling of 5 ml (for realization of a basophil activation test) and a blood sampling of 250 ml

Diagnostic Test: IgG group

IgE group

OTHER

Patient in the IgE will benefit from a blood sampling of 5 ml (for realization of a basophil activation test) and a bone marrow sampling (approx 2 ml)

Diagnostic Test: IgE group

IgG group + IgE group

OTHER

Patient in the IgG + IgE will benefit from a blood sampling of 5 ml (for realization of a basophil activation test), a blood sampling of 250 ml and a bone marrow sampling (approx 2 ml)

Diagnostic Test: IgG group + IgE group

Interventions

IgG group DIAGNOSTIC_TEST

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

IgG group

IgE group DIAGNOSTIC_TEST

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

IgE group

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

IgG group + IgE group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Common to both groups:
• 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
• For IgE group:
• \- presence of at least one positive skin test to one of the suspected agent (curare and/or antibiotic) during the allergist consultation
• For the IgG group:
• \- presence of circulating IgG-type antibodies directed against one of the suspected agents (curare, antibiotic, antiseptic), identified in the routine biological tests carried out at the time of the shock and / or the consultation of allergology.

You may not qualify if:

• Common to both groups:
• Absence of written informed consent
• Protected person: under guardianship or curatorship
• Patient without social security
• Pregnancy of breast feeding
• Ongoing immunosuppressive or chemotherapy
• Acute heart failure
• For IgE group:
• Taking oral or injectable anticoagulants
• Taking a double antiplatelet aggregation
• Previous sternotomy
• Previous thoracic radiation therapy
• Known allergy to local anesthesic or iodinated skin products
• Previous major sternal cutaneous lesions
• Prerequisites for carrying out the sternal sample in order to carry out a myelogram (IgE group):

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut Pasteur: collaborator

Study Sites (1)

Hôpital Bichat claude Bernard

Paris, Paris, 75018, France

RECRUITING

MeSH Terms

Conditions

Hypersensitivity, Immediate; Hypersensitivity; Epilepsy, Idiopathic Generalized; Anaphylaxis

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Aurelie Gouel, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aurelie Gouel, MD, PhD

CONTACT

00-33-1-40-25-83-55; aurelie.gouel@aphp.fr

Pierre Bruhns, PhD

CONTACT

00-33-1-45-68-86-29; bruhns@pasteur.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2022
• First Posted: June 15, 2022
• Study Start: April 12, 2023
• Primary Completion (Estimated): April 12, 2033
• Study Completion (Estimated): December 15, 2033
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)