Humoral Primary Immunodeficiencies (PIDs)EVAHNCT06659588
Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency
An observational study of Humoral Primary Immunodeficiencies (PIDs) and Secondary Form of Humoral Immunodeficiencies, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Humoral Primary Immunodeficiencies (PIDs), Secondary Form of Humoral Immunodeficiencies, Combined Immunodeficiency (CID)
- What is being tested?
- Plasma, urine and stool collection
- How many people
- 200 participants
- Where
- 3 sitesFrance
- Study dates
- 10 Oct 2024to 3 Sep 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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).
Who may be able to join
- 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)
Who cannot join
- Patients not belonging to one of the target populations
- Opposition of legal representatives of minor patients, patients themselves and adult patients
Trial locations and contacts
3 sites in 1 country.
France3 sites
Hôpital Saint-Louis
Paris, 75010
Hôpital Cochin
Paris, 75014
Hôpital Necker-Enfants Malades
Paris, 75015
About this study
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:
Read more
- 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.
Read the 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)
- Being tested
- Plasma, urine and stool collection
- 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
- Medical subject headings
- Severe Combined Immunodeficiency, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma, urine and stool collectionOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: 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. Receives: 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). Receives: Other: Plasma, urine and stool collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Measured: Day 0
Secondary outcomes (8)
Description of characteristics of primary immunodeficiency of patients presenting enteric virus associated hepatitis (EVAH)
Clinico-biological characterization of patients presenting enteric virus associated hepatitis (EVAH) based on characteristics of immunodeficiency .
- Genetic mutation or previous immunosupressor treatment
- Plasma concentration of immunoglobulin in g/L
- Lymphocytes (total and subpopulation) count in number of cells/mm3
- Serological responses to antigen or vaccination : positive or negative
Patients will be clustered in 4 cohorts :
- Humoral primary deficiency
- Secondary form of humoral immunodeficiencies
- Combined immunodeficiency
- Severe combined immunodeficiency Prevalence of EVAH patients will be evaluated in each subgroup
Measured: Day 0
Description of global impact of chronic viral infection
Global impact of chronic viral infection will be evaluated by a clinical score including :
- Clinical state alteration by Lansky score
- BMI in kg/m^2
- weight loss in kg
- height stagnation in cm
- chronic diarrhoea in number of watery stool/day
- chronic abdominal pain : present or absent
- presence of fever : present or absent
- presence of neurological abnormalities : present or absent, description
- haematological biological parameters : blood cells counts
- renal function : creatinine blood concentration in µmol/L, Urea blood concentration in mmol/L, ionic blood concentration in mmol/L
- Protein blood concentration in g/L
- Presence of portal hypertension : presence or absence
- presence of hepato-pulmonary syndrome : presence or absence The parameter will be compared between EVAH+ and EVAH- patients.
Measured: Day 0
Microbiological characterization of patients presenting enteric virus associated hepatitis (EVAH)
The parameters will be compared between EVAH+ and EVAH- patients.
Rate of patients with :
- enteric virus in stools : presence or absence
- enteric virus in urine : presence or absence
- enteric virus in plasma : presence or absence
- enteric virus in organ biopsies : presence or absence
Measured: Day 0
Anatomic-pathologic characterization of patients presenting enteric virus associated hepatitis (EVAH)
The parameters will be compared between EVAH+ and EVAH- patients. Rate of patient with histologically proven
- nodular regenerative hyperplasia : presence or absence
- liver infiltrating T cell lymphocytes : presence or absence
Measured: Day 0
Descrition of immunological characterization of patients presenting enteric virus associated hepatitis (EVAH)
The percentage of CD3+CD8+HLA-DRhigh CD38high CD127low will be mesured. The parameter will be compared between EVAH+ and EVAH- patients.
Measured: Day 0
Phenotypically characterize the cellular response in EVAH patients
Characterize the immunological process associated with EVAH syndrome.
The parameter will be compared between different cohorts of patients:
- Percent (%) of leukocytes subpopulation in circulating blood by CyTOF
Measured: Day 0
Transcriptionally characterize the cellular response in EVAH patients
Characterize the immunological process associated with EVAH syndrome. For a subgroup of representative patients (EVAH+ and EVAH-) the circulating leukocyte populations will be studied using single-cell RNA sequencing (scRNASeq).
Comparison between different cohorts of patients.
Measured: Day 0
Specific anti-viral responses in patients presenting enteric virus associated hepatitis (EVAH)
Identification and characterization of specific anti-viral cellular responses by specific pentamers and elispot in EVAH patients.
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2024
- Study start10 Oct 2024
- Primary completion3 Sep 2026
- Study completion3 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Humoral Primary Immunodeficiencies (PIDs)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Victor Michel, MD, Principal investigator, Assistance Publique - Hôpitaux de ParisBénédicte Neven, MD, PhD, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06659588
- Sponsor's protocol ID
- APHP231054
- Other IDs
- 2022-A02615-38
- Acronym
- EVAH
- Status last verified
- Sep 2026
- First submitted
- 15 Feb 2024
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36638922Klocperk 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.
PubMed 35589883Strohmeier 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.
PubMed 36282455Fourgeaud 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.
PubMed 37078608
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06659588
- Acronym / sponsor ID
- EVAH / APHP231054
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 10 Oct 2024 (actual)
- Primary completion
- 3 Sep 2026 (actual)
- Study completion
- 3 Sep 2026 (actual)
- First posted
- 26 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Humoral primary immunodeficiencies (PIDs) | – | Other: Plasma, urine and stool collectionPatients 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. |
| Secondary form of humoral immunodeficiencies | – | Other: Plasma, urine and stool collectionPatients 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). |
| Combined immunodeficiency (CID) | – | Other: Plasma, urine and stool collectionPatients 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. |
| Severe combined immunodeficiency (SCID) | – | Other: Plasma, urine and stool collectionPatients 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). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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).
Key inclusion criteria (7 listed)
- Information and non-opposition from the legal representatives of minor patients, the patients themselves and adult patients of the 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
Key exclusion criteria (2 listed)
- Patients not belonging to one of the target populations
- Opposition of legal representatives of minor patients, patients themselves and adult patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasma, urine and stool collectionDuring 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. | Other | Combined immunodeficiency (CID), Humoral primary immunodeficiencies (PIDs), Secondary form of humoral immunodeficiencies, Severe combined immunodeficiency (SCID) |
Primary outcome
Number of patients with chronic hepatic and/or digestive abnormalities
Time frame: Day 0
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.
Number of patients with an identified enteric virus
Time frame: Day 0
The number of patients with an enteric virus identified in stools, and/or urine, plasma, organ biopsies and the type of enteric virus identified.
Statistical association between chronic hepatic and/or digestive abnormalities and enteric virus infection
Time frame: Day 0
We will use the homogeneity test Chi-square to compare the distribution of enteric virus groups (EVAH and controls).
8 secondary outcomes
Description of characteristics of primary immunodeficiency of patients presenting enteric virus associated hepatitis (EVAH)
Time frame: Day 0
Description of global impact of chronic viral infection
Time frame: Day 0
Microbiological characterization of patients presenting enteric virus associated hepatitis (EVAH)
Time frame: Day 0
Anatomic-pathologic characterization of patients presenting enteric virus associated hepatitis (EVAH)
Time frame: Day 0
Descrition of immunological characterization of patients presenting enteric virus associated hepatitis (EVAH)
Time frame: Day 0
Phenotypically characterize the cellular response in EVAH patients
Time frame: Day 0
Transcriptionally characterize the cellular response in EVAH patients
Time frame: Day 0
Specific anti-viral responses in patients presenting enteric virus associated hepatitis (EVAH)
Time frame: Day 0
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Background: PubMed 36638922Riller 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.
- Background: PubMed 35589883Klocperk 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.
- Background: PubMed 36282455Strohmeier 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.
- Background: PubMed 37078608Fourgeaud 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Victor Michel, MD principal investigator
Assistance Publique - Hôpitaux de Paris
Bénédicte Neven, MD, PhD study director
Assistance Publique - Hôpitaux de Paris
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Humoral Primary Immunodeficiencies (PIDs) and Secondary Form of Humoral Immunodeficiencies, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with chronic hepatic and/or digestive abnormalities (time frame: Day 0). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06659588, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.