Determine Immunoglobulin G4 (IgG4) Standards for Cow's Milk and Egg in Different Populations of Allergic and Non-allergic Children

NCT ID: NCT03776474

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-11-18
• Study Completion Date: 2025-11-18

Brief Summary

The study objectives are :

Determine standards of plasma levels of casein-specific immunoglobulin G4 (IgG4) and egg-specific immunoglobulin G4 (IgG4) as a function of age, in non-allergic children, in allergic children, and in cured former allergic patients.

Analyze the plasma IgG4 / IgE ratio, according to the result of the oral provocation test (tolerance versus allergy) and, in the event of a reaction, according to the reactogenic dose (dose which caused the reaction).Determine whether analysis of the plasma metabolome can identify children with a cured allergy to cow's milk protein or to egg from those with a persistent allergy.

Detailed Description

Immunoglobulin E (IgE) mediated allergies to cow's milk and hen's egg affects 2-3% and 0.5-2.5% of children respectively. These allergies expose to the risk of immediate anaphylactic reaction that may be life-threatening. Approximately 70-80% of children with IgE mediated allergies to cow's milk and hen's egg will tolerate these foods by the age of 6 years. However, in the absence of reliable biomarker of tolerance, to determine whether oral tolerance is obtained, it is recommended to perform an oral food challenge (OFC) in a hospital setting. This procedure is expensive, time consuming, and carries the risk of anaphylactic reactions. Many studies have tried to find predictive markers of reactivity during the OFC. Improving the prediction of the response to OFC would be very useful to better select children in whom an OFC can be performed without risk to confirm the acquisition of tolerance.

For instance, serum specific IgE positive values beyond which 95% of patients would have an allergic reaction have been proposed. These values are highly variable from one study to another because of methodological differences and heterogeneity of populations, and cannot be used in clinical practice.

The regular dosage of serum specific IgE and its evolution over time is used in clinical practice to predict a possible persistence of IgE mediated food allergy. Indeed, an initial high rate and/or elevation of specific IgE levels may be predictive of a persistent allergy, while initial low rates and a decrease in specific IgE may predict tolerance. When tolerance develops, there is a decrease in specific IgE levels, however, even if tolerance is obtained, they can remain positive at pathological levels.

During continuous exposure to an allergen, the specific immunoglobulin G4 (IgG4) response is physiological. Oral immunotherapy studies in food allergies showed an elevation of specific IgG4, associated with an elevation in the number of regulatory T lymphocytes (LTreg) and the production of interleukin (IL)-10. The development of spontaneous oral tolerance, without the intervention of immunotherapy, also seems to involve IgG4. In a prospective follow-up of a cohort of children with an IgE-mediated cow's milk allergy, the elevation of specific IgG4 was observed in those who cure of their allergy, with rates higher than those observed in children whose allergy persists. In children with cow's milk and/or egg allergies, a low concentration of specific (IgG4 of B-Lactoglobulin or ovalbumin is associated with the need for a more prolonged exclusion diet. The balance between specific IgE and IgG4 therefore appears to be important in the development of tolerance and may reflect the balance between effector T cells and LTreg. However, the normal serum levels of IgG4 to cow's milk and hen's egg are unknown.

A recently published study of Doctor Guillaume Lezmi and Professor Karine Adel-Patient shows that children with an IgE-mediated allergy to cow's milk protein and those who outgrew this allergy, have distinct plasma metabolomic signature. This suggests that plasma metabolomic analysis may be a useful too to differentiate children with a persistent cow's milk protein allergy from those who acquired tolerance to cow's milk. If confirmed, the metabolic signature may be useful to better identify children to whom an oral food challenge with cow's milk protein could be propose. These results need to be confirmed in a larger population and in other food allergies.

The study objectives are :

Determine standards of plasma levels of casein-specific immunoglobulin G4 (IgG4) and egg-specific immunoglobulin G4 (IgG4) as a function of age, in non-allergic children, in allergic children, and in cured former allergic patients.

Analyze the plasma IgG4 / IgE ratio, according to the result of the oral provocation test (tolerance versus allergy) and, in the event of a reaction, according to the reactogenic dose (dose which caused the reaction).

Determine whether analysis of the plasma metabolome can identify children with a cured allergy to cow's milk protein or to egg from those with a persistent allergy.

Conditions

Food Allergy in Children

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Allergic

Minors allergic to cow's milk and/or eggs

Blood collection

Intervention Type: BIOLOGICAL

Patients less than 5 kg : 2 ml Patients over 5 kg : 3 ml Patients over 10 kg : 5 ml

Non-allergic

Minors without history of allergy to cow's milk and/or eggs

Blood collection

Intervention Type: BIOLOGICAL

Patients less than 5 kg : 2 ml Patients over 5 kg : 3 ml Patients over 10 kg : 5 ml

Acquired tolerance

Minors formerly allergic to cow's milk and/or eggs

Blood collection

Intervention Type: BIOLOGICAL

Patients less than 5 kg : 2 ml Patients over 5 kg : 3 ml Patients over 10 kg : 5 ml

Interventions

Blood collection

Patients less than 5 kg : 2 ml Patients over 5 kg : 3 ml Patients over 10 kg : 5 ml

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Minors aged 0 to 18
• In consultation or hospitalized for an oral food challenge for milk or eggs
• To undergo a blood test

Exclusion Criteria

Minors with immune deficiency, chronic inflammatory disease or immunosuppressive or immunomodulator treatment

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillaume Lezmi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Necker Enfants malades

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Guillaume Lezmi, MD, PhD

Role: CONTACT

guillaume.lezmi@aphp.fr

+33 1 44 49 48 38

Hélène Morel

Role: CONTACT

helene.morel@aphp.fr

+33 1 71 19 63 46

Facility Contacts

Guillaume Lezmi, MD, PhD

Role: primary

guillaume.lezmi@aphp.fr

+33 1 44 49 48 38

Hélène Morel

Role: backup

helene.morel@aphp.fr

+33 1 71 19 63 46

References

Adel-Patient K, Lezmi G, Castelli FA, Blanc S, Bernard H, Soulaines P, Dumond P, Ah-Leung S, Lageix F, de Boissieu D, Cortes-Perez N, Hazebrouck S, Fenaille F, Junot C, Dupont C. Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow's milk. Clin Transl Allergy. 2018 Sep 28;8:38. doi: 10.1186/s13601-018-0224-9. eCollection 2018.

Reference Type: BACKGROUND

PMID: 30275944 (View on PubMed)

Other Identifiers

2018-A01972-53

Identifier Type: REGISTRY

Identifier Source: secondary_id

APHP180057

Identifier Type: -

Identifier Source: org_study_id