Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency

NCT ID: NCT06659588

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-10-10
• Study Completion Date: 2026-10-10

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).

Conditions

Humoral Primary Immunodeficiencies (PIDs); Secondary Form of Humoral Immunodeficiencies; Combined Immunodeficiency (CID); Severe Combined Immunodeficiency (SCID)

Study Design

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

Study Groups

Humoral primary immunodeficiencies (PIDs)

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.

Plasma, urine and stool collection

Intervention Type: OTHER

During a consultation for follow-up, we will take an extra-volume during a blood sample taken as part of the care. We will also collect stool and urine.

There will be no biological collection for these samples. Organ biopsies carried out as part of the care (liver, kidney, digestive tract, spleen, lymph node) will also be studied as part of this research.

Secondary form of humoral immunodeficiencies

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 a 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).

Plasma, urine and stool collection

Intervention Type: OTHER

During a consultation for follow-up, we will take an extra-volume during a blood sample taken as part of the care. We will also collect stool and urine.

There will be no biological collection for these samples. Organ biopsies carried out as part of the care (liver, kidney, digestive tract, spleen, lymph node) will also be studied as part of this research.

Combined immunodeficiency (CID)

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 a combined immunodeficiency.

Plasma, urine and stool collection

Intervention Type: OTHER

During a consultation for follow-up, we will take an extra-volume during a blood sample taken as part of the care. We will also collect stool and urine.

There will be no biological collection for these samples. Organ biopsies carried out as part of the care (liver, kidney, digestive tract, spleen, lymph node) will also be studied as part of this research.

Severe combined immunodeficiency (SCID)

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 a severe combined immunodeficiency beyond 2 years post cell therapy (allogeneic haematopoietic stem cell transplantation (aHSCT) or gene therapy).

Plasma, urine and stool collection

Intervention Type: OTHER

During a consultation for follow-up, we will take an extra-volume during a blood sample taken as part of the care. We will also collect stool and urine.

There will be no biological collection for these samples. Organ biopsies carried out as part of the care (liver, kidney, digestive tract, spleen, lymph node) will also be studied as part of this research.

Interventions

Plasma, urine and stool collection

During a consultation for follow-up, we will take an extra-volume during a blood sample taken as part of the care. We will also collect stool and urine.

There will be no biological collection for these samples. Organ biopsies carried out as part of the care (liver, kidney, digestive tract, spleen, lymph node) will also be studied as part of this research.

Intervention Type: OTHER

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

• 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

Victor Michel, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Bénédicte Neven, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Saint-Louis

Paris, , France

Site Status: RECRUITING

Hôpital Cochin

Paris, , France

Site Status: RECRUITING

Hôpital Necker-Enfants Malades

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Victor Michel, MD

Role: CONTACT

victor.michel@institutimagine.org

1 42 75 44 35 ext. +33

Hélène Morel

Role: CONTACT

helene.morel@aphp.fr

1 71 19 63 46

Facility Contacts

Marion MALPHETTES, MD

Role: primary

Georgia MALAMUT, MD, PhD

Role: primary

Victor Michel, MD

Role: primary

victor.michel@institutimagine.org

1 42 75 44 35 ext. +33

References

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Reference Type: BACKGROUND

PMID: 36638922 (View on PubMed)

Klocperk A, Friedmann D, Schlaak AE, Unger S, Parackova Z, Goldacker S, Sediva A, Bengsch B, Warnatz K. Distinct CD8 T Cell Populations with Differential Exhaustion Profiles Associate with Secondary Complications in Common Variable Immunodeficiency. J Clin Immunol. 2022 Aug;42(6):1254-1269. doi: 10.1007/s10875-022-01291-9. Epub 2022 May 19.

Reference Type: BACKGROUND

PMID: 35589883 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 36282455 (View on PubMed)

Fourgeaud J, Lecuit MM, Perot P, Bruneau J, Regnault B, Da Rocha N, Bessaud M, Picard C, Jeziorski E, Fournier B, Levy R, Marcais A, Blanche S, Frange P, Fischer A, Cavazzana M, Ferroni A, Jamet A, Leruez-Ville M, Eloit M, Neven B. Chronic Aichi Virus Infection As a Cause of Long-Lasting Multiorgan Involvement in Patients With Primary Immune Deficiencies. Clin Infect Dis. 2023 Aug 22;77(4):620-628. doi: 10.1093/cid/ciad237.

Reference Type: BACKGROUND

PMID: 37078608 (View on PubMed)

Other Identifiers

2022-A02615-38

Identifier Type: OTHER

Identifier Source: secondary_id

APHP231054

Identifier Type: -

Identifier Source: org_study_id