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

NCT06659588 | Recruiting

• 2 other identifiers: APHP2310542022-A02615-38
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 3

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.

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

Outcome Measures

Primary Outcomes (3)

• Number of patients with chronic hepatic and/or digestive abnormalities

  Number of patients with : * Chronic hepatitis (\> 6 months with an increase in aspartate-aminotransferase/alanine-aminotransferase transaminases and/or gamma-glutamyl-transpeptidase levels greater than 2 times the upper limit of normal) without an identified cause (negative hepatotropic autoantibodies test and absence of infection by hepatitis viruses A, B, C, E). * Or histologically proven nodular regenerative hyperplasia. * And/or chronic enteropathy of undetermined etiology.

  Day 0

• Number of patients with an identified enteric virus

  The number of patients with an enteric virus identified in stools, and/or urine, plasma, organ biopsies and the type of enteric virus identified.

  Day 0

• Statistical association between chronic hepatic and/or digestive abnormalities and enteric virus infection

  We will use the homogeneity test Chi-square to compare the distribution of enteric virus groups (EVAH and controls).

  Day 0

Secondary Outcomes (8)

• Description of characteristics of primary immunodeficiency of patients presenting enteric virus associated hepatitis (EVAH)

  Day 0

• Description of global impact of chronic viral infection

  Day 0

• Microbiological characterization of patients presenting enteric virus associated hepatitis (EVAH)

  Day 0

• Anatomic-pathologic characterization of patients presenting enteric virus associated hepatitis (EVAH)

  Day 0

• Descrition of immunological characterization of patients presenting enteric virus associated hepatitis (EVAH)

  Day 0

Study Arms (4)

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.

Other: Plasma, urine and stool collection

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).

Other: Plasma, urine and stool collection

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.

Other: Plasma, urine and stool collection

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).

Other: Plasma, urine and stool collection

Interventions

Plasma, urine and stool collection 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); Humoral primary immunodeficiencies (PIDs); Secondary form of humoral immunodeficiencies; Severe combined immunodeficiency (SCID)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• \- 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)

You may not qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (3)

Hôpital Saint-Louis

Paris, 75010, France

RECRUITING

Hôpital Cochin

Paris, 75014, France

RECRUITING

Hôpital Necker-Enfants Malades

Paris, 75015, France

RECRUITING

Related Publications (4)

• Riller Q, Fourgeaud J, Bruneau J, De Ravin SS, Smith G, Fusaro M, Meriem S, Magerus A, Luka M, Abdessalem G, Lhermitte L, Jamet A, Six E, Magnani A, Castelle M, Levy R, Lecuit MM, Fournier B, Winter S, Semeraro M, Pinto G, Abid H, Mahlaoui N, Cheikh N, Florkin B, Frange P, Jeziorski E, Suarez F, Sarrot-Reynauld F, Nouar D, Debray D, Lacaille F, Picard C, Perot P, Regnault B, Da Rocha N, de Cevins C, Delage L, Perot BP, Vinit A, Carbone F, Brunaud C, Marchais M, Stolzenberg MC, Asnafi V, Molina T, Rieux-Laucat F, Notarangelo LD, Pittaluga S, Jais JP, Moshous D, Blanche S, Malech H, Eloit M, Cavazzana M, Fischer A, Menager MM, Neven B. Late-onset enteric virus infection associated with hepatitis (EVAH) in transplanted SCID patients. J Allergy Clin Immunol. 2023 Jun;151(6):1634-1645. doi: 10.1016/j.jaci.2022.12.822. Epub 2023 Jan 10.

  PMID: 36638922 BACKGROUND

• 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.

  PMID: 35589883 BACKGROUND

• Strohmeier V, Andrieux G, Unger S, Pascual-Reguant A, Klocperk A, Seidl M, Marques OC, Eckert M, Grawe K, Shabani M, von Spee-Mayer C, Friedmann D, Harder I, Gutenberger S, Keller B, Proietti M, Bulashevska A, Grimbacher B, Provaznik J, Benes V, Goldacker S, Schell C, Hauser AE, Boerries M, Hasselblatt P, Warnatz K. Interferon-Driven Immune Dysregulation in Common Variable Immunodeficiency-Associated Villous Atrophy and Norovirus Infection. J Clin Immunol. 2023 Feb;43(2):371-390. doi: 10.1007/s10875-022-01379-2. Epub 2022 Oct 25.

  PMID: 36282455 BACKGROUND

• 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.

  PMID: 37078608 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma Feces Urine

MeSH Terms

Conditions

Severe Combined Immunodeficiency; Inflammatory Bowel Diseases

Interventions

Urination

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Urinary Tract Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Victor Michel, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Bénédicte Neven, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Central Study Contacts

Victor Michel, MD

CONTACT

1 42 75 44 35; victor.michel@institutimagine.org

Hélène Morel

CONTACT

1 71 19 63 46; helene.morel@aphp.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2024
• First Posted: October 26, 2024
• Study Start: October 10, 2024
• Primary Completion (Estimated): October 10, 2026
• Study Completion (Estimated): October 10, 2026
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)