Genetic Susceptibility to Severe Infections

NCT ID: NCT06102070

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 2000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-02-18
• Study Completion Date: 2038-10-18

Brief Summary

Only a fraction of individuals infected with microbes develop clinical disease. This observation raises fundamental questions about the pathogenesis of infectious diseases. There is a complex interaction between environmental (microbial and non-microbial) and human (genetic and non-genetic) factors. This will determine the quality of the immune response against the infectious agent and the clinical manifestation. By definition, individuals who die from an infection have defective immunity to the pathogen in question (immune agent (immune deficiency).

The investigation of individual variability in the development of infectious diseases began in the early 20th. The first evidence to support the hypothesis that individual variability variability and immune deficiencies were hereditary came from observations of familial cases or genetic isolates genetic isolates (from a homogeneous population) of rare or common infectious diseases, which in some cases Mendelian heredity hat predisposition to infectious diseases runs in families even more so than diseases associated with less determined environmental factors, such as certain cancers. such as certain cancers. Finally, studies comparing the rate of concordance of infectious diseases between monozygotic and dizygotic twins also implicate genetic factors in disease susceptibility.

These observations were validated by the discovery of genetic defects associated with severe infectious diseases, leading to proof of concept. While a number of hereditary immune deficiencies associated with susceptibility to multiple pathogens or microorganisms, a growing number of new and rare new and rare immune deficiencies conferring restricted susceptibility to infections caused by a single caused by a single pathogen family, or even a single pathogen, in otherwise healthy children, have recently been identified (one gene, one pathogen). As a result, a dozen Mendelian clinical syndromes characterized by restricted susceptibility are now known. Over the last 20 years, it has been proven that these "idiopathic" infections were immune deficiencies.

The investigators now wish to study new severe infections, including but not limited to viral, fungal and bacterial infections. viral, fungal, bacterial and parasitic infections. This should lead to a better understanding of the pathophysiology of each disease, the development of new therapeutics and better patient care.

Detailed Description

Justification of the number of subjects:

The prevalence of the various severe infections we wish to explore ranges from one case in 50,000 to one case in 1,000,000 individuals; consequently, we plan to recruit only a small cohort of patients per pathology. Due to the exploratory nature of this research, no sample size calculation is possible.

ELIGIBILITY CRITERIA

Inclusion criteria :

1. Index cases (patients)

• Informed consent signed by the patient. In the case of a minor patient, consent must be signed by the holders of parental authority. In the case of a protected adult patient, consent is signed by his or her signed by the patient's legal representative. In the case of an adult patient unable to consent at the time of consent is signed by a family member.
• have a proven rare and severe infection defined by at least one of the following elements:

• Acute, life-threatening infection requiring hospitalization, especially in an intensive particularly in intensive care.
• Recurrent and/or chronic infections requiring frequent hospitalization or follow-up visits hospitalization or follow-up visits (dermatology, cardiology, neurology, infectious diseases, immunology, etc.), infectious diseases, immunology, etc.).
• Acute and/or chronic infections leading to sequelae (motor or cognitive deficits, etc.).
• Disseminated infection by an opportunistic microbe.
• be hospitalized or followed in a specialized hospital ward, emergency room or intensive care unit
• be affiliated to a Social Security scheme.

2. Related

• have informed consent signed by the adult relative. In the case of a minor relative, the consent is consent is signed by the holders of parental authority. In the case of an adult relative the consent is signed by his or her legal representative
• be related to the index case up to the 3rd degree: Parents, Children, Brother, Sister, Grandparents, Uncles, Aunts, Cousins, Nephews, Nieces
• be affiliated to a Social Security system

Non-inclusion criteria :

1. Index case:4/4 C18-41 _Predisposition_Synopsis_V2.0_20220324

• Acquired immunodeficiency (having received immunosuppressive treatment in the 3 months prior to the onset of the disease or HIV-positive)
• Pregnant at the time of illness
• Person under court protection

2. Related persons :

• Pregnant or breast-feeding woman
• Person under court protection

Conditions

Infectious Disease

Study Design

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

Study Groups

Predisposition

individuals suffering of having previously suffered of severe infectious diseases

Blood samples drawing

Intervention Type: OTHER

10 ml of periferal blood

Skin biopsy

Intervention Type: OTHER

Skin biopsy only in some index cases depending of the pathology at the recruitment

Interventions

Blood samples drawing

10 ml of periferal blood

Intervention Type: OTHER

Skin biopsy

Skin biopsy only in some index cases depending of the pathology at the recruitment

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• to sign the informed consent signed by the patient. In the case of a minor patient, consent is signed by the holders of parental authority. In the case of a protected adult patient, the consent is signed by their legal representative. In the case of an adult patient unable to consent at the time of inclusion, consent is signed by a family member.
• to have a proven rare and severe infection
• to be hospitalized or followed in a specialized hospital department, in the emergency room or in intensive care
• to be affiliated to the French Social Security system
• for relatives, to be related to the index case up to the 3rd degree: Parents, Children, Brother, Sister, Grandparents, Uncles, Aunts, Cousins, Nephews, Nieces

Exclusion Criteria

• to have an acquired immunodeficiency (having received immunosuppressive treatment in the 3 months preceding the onset of the disease or being HIV positive)
• pregnant woman at the time of illness

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre d'Etudes des Déficits Immunitaires (CEDI), Hôpital Necker-Enfants

Paris, Île-de-France Region, France

Site Status: RECRUITING

Countries

France

Central Contacts

Jacinta Md BUSTAMANTE, MD-PhD

Role: CONTACT

jacinta.bustamante@aphp.fr

01 71 19 60 04

Facility Contacts

jacinta MD BUSTAMANTE, MD-PHD

Role: primary

jacinta.bustamante@aphp.fr

0171196004

Other Identifiers

C18-41

Identifier Type: -

Identifier Source: org_study_id