Clinical trial NCT06659588: Study of Populations At Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients with Primary Immunodeficiency and Secondary Humoral Deficiency
Official title: Study of Populations At Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients with Primary Immunodeficiency and Secondary Humoral Deficiency
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Humoral Primary Immunodeficiencies (PIDs)
Secondary Form of Humoral Immunodeficiencies
Combined Immunodeficiency (CID)
Severe Combined Immunodeficiency (SCID)
Keywords: Humoral primary immunodeficiencies (PIDs)
Secondary form of humoral immunodeficiencies
Combined immunodeficiency (CID)
Severe combined immunodeficiency (SCID)
Nodular regenerative hyperplasia
Chronic enteropathy
Enteric virus associated hepatitis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-10-26
Enrollment: 120
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with no age limit followed in one of the skills centers of the Reference Center for Hereditary Immune Deficits (CEREDIH) within the APHP (Necker-Enfants Malades Hospital, Saint-Louis Hospital and Cochin Hospital) for humoral primary immunodeficiencies (PIDs), secondary form of humoral immunodeficiencies, combined immunodeficiency (CID), severe combined immunodeficiency (SCID).

Brief summary: Dysimmune and specially hepatic immuno-pathological processes are frequent in patients with PIDs (primary immune deficiencies), particularly but not exclusively in patients with humoral defects. In the latter, nodular regenerative hyperplasia is a frequent complication. It is often associated with mislabeled chronic enteropathy. The investigators hypothesized that chronic viral infection with an enteric virus and the immune response that it implies might explain these processes.

To identify populations at risk of EVAH (enteric virus-associated hepatitis), four cohorts of patients will be studied:

* Primary humoral immune deficiencies
* Secondary humoral immune deficiencies (following anti-CD20 monoclonal antibodies, CAR-T cells)
* Combined immunodeficiencies
* Severe combined immunodeficiency syndrome (SCID) after allograft with humoral defect The investigators will collect clinical, biological and genetic information and features related to immunological responses and inflammatory damage for these patients. The investigators will include EVAH suspected patients and control patients in each cohort.

The investigators will take additional blood, stool and urine samples during the same time as the samples taken for the care.

The investigators will carry out tests for enteric viruses screening on stool, urine and plasma. The investigators will perform the viral screening on organ biopsies taken as part of the care.

A subgroup of representative patients (EVAH+ and EVAH-) will benefit from ancillary studies to characterize the leukocyte populations in the circulating blood and the immune response for these processes. In EVAH patients, the investigators will study specific anti-viral cellular response.

Detailed description: Dysimmune and specially hepatic immuno-pathological processes are frequent in patients with PIDs (primary immune deficiencies), particularly but not exclusively in patients with humoral defects. In the latter, nodular regenerative hyperplasia is a frequent complication. It is often associated with mislabeled chronic enteropathy. The investigators hypothesized that chronic viral infection with an enteric virus and the immune response that it implies might explain these processes.

To identify populations at risk of EVAH (enteric virus-associated hepatitis), four cohorts of patients will be studied:

* Primary humoral immune deficiencies
* Secondary humoral immune deficiencies (following anti-CD20 monoclonal antibodies, CAR-T cells)
* Combined immunodeficiencies
* Severe combined immunodeficiency syndrome (SCID) after allograft with humoral defect The investigators will collect clinical, biological and genetic information and features related to immunological responses and inflammatory damage for these patients. The investigators will include EVAH suspected patients and control patients in each cohort.

The investigators will take additional blood, stool and urine samples during the same time as the samples taken for the care.

The investigators will carry out tests for enteric viruses screening on stool, urine and plasma by multiplex RT-PCR (Norovirus GI, Norovirus GII, Rotavirus, Sapovirus, and Astrovirus) and by targeted PCR (Enterovirus, Adenovirus, Aichi virus, Parechovirus, Kobuvirus and Astrovirus MLB1) on plasma and urine. The investigators will perform the viral screening on organ biopsies (liver, kidney, digestive tract, spleen, lymph node) taken as part of the care by mNGS (Metagenomics Next Generation Sequencing).

A subgroup of representative patients (EVAH+ and EVAH-) will benefit from ancillary studies to characterize the leukocyte populations in the circulating blood and the immune response for these processes. In EVAH patients, the investigators will study specific anti-viral cellular response by specific pentamers and elispot (enzyme-linked immunospot).

Eligibility criteria: Inclusion Criteria:

- Information and non-opposition from the legal representatives of minor patients, the patients themselves and adult patients of the population of interest.

Population of interest:

Patients with no age limit followed in one of the skills centers of the Reference Center for Hereditary Immunodeficiencies (CEREDIH) within the APHP (Necker-Enfants Malades hospital, Saint-Louis Hospital and Cochin hospital) and presenting:

* Humoral primary immunodeficiencies (PIDs) defined according to the IUIS (International Union of Immunological Societies) criteria
* Secondary form of humoral immunodeficiencies (post anti-CD20 monoclonal antibody or post CAR-T cells therapy with alymphocytosis B and/or hypo IgA or IgM or IgG)
* Combined immunodeficiency (CID) defined according to the IUES criteria
* Severe combined immunodeficiency (SCID) beyond 2 years post cell therapy (allogeneic haematopoietic stem cell transplantation (aHSCT) or gene therapy)

Exclusion Criteria:

* Patients not belonging to one of the target populations
* Opposition of legal representatives of minor patients, patients themselves and adult patients

Primary outcomes:
measure: Number of patients with chronic hepatic and/or digestive abnormalities
timeFrame: Day 0
measure: Number of patients with an identified enteric virus
timeFrame: Day 0
measure: Statistical association between chronic hepatic and/or digestive abnormalities and enteric virus infection
timeFrame: Day 0
Secondary outcomes:
measure: Description of characteristics of primary immunodeficiency of patients presenting enteric virus associated hepatitis (EVAH)
timeFrame: Day 0
measure: Description of global impact of chronic viral infection
timeFrame: Day 0
measure: Microbiological characterization of patients presenting enteric virus associated hepatitis (EVAH)
timeFrame: Day 0
measure: Anatomic-pathologic characterization of patients presenting enteric virus associated hepatitis (EVAH)
timeFrame: Day 0
measure: Descrition of immunological characterization of patients presenting enteric virus associated hepatitis (EVAH)
timeFrame: Day 0
measure: Phenotypically characterize the cellular response in EVAH patients
timeFrame: Day 0
measure: Transcriptionally characterize the cellular response in EVAH patients
timeFrame: Day 0
measure: Specific anti-viral responses in patients presenting enteric virus associated hepatitis (EVAH)
timeFrame: Day 0
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Victor Michel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Bénédicte Neven, MD, PhD
role: STUDY_DIRECTOR
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