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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-A02615-38 | Other Identifier | IDRCB Number |
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| Name | Class |
|---|---|
| URC-CIC Paris Descartes Necker Cochin | OTHER |
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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:
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.
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:
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| |
| 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). |
| |
| 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. |
| |
| 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). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with chronic hepatic and/or digestive abnormalities | Number of patients with :
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 .
Patients will be clustered in 4 cohorts :
|
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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:
Exclusion Criteria:
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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).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Victor Michel, MD | Contact | 1 42 75 44 35 | +33 | victor.michel@institutimagine.org |
| Hélène Morel | Contact | 1 71 19 63 46 | helene.morel@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Victor Michel, MD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Bénédicte Neven, MD, PhD | Assistance Publique - Hôpitaux de Paris | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Saint-Louis | Recruiting | Paris | 75010 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36638922 | Background | 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. | |
| 35589883 |
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Plasma Feces Urine
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|
| Day 0 |
| Description of global impact of chronic viral infection | Global impact of chronic viral infection will be evaluated by a clinical score including :
| 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 :
| 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
| 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. | 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 | 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. | 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. | Day 0 |
| Hôpital Cochin | Recruiting | Paris | 75014 | France |
|
| Hôpital Necker-Enfants Malades | Recruiting | Paris | 75015 | France |
|
| 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. |
| 36282455 | 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. |
| 37078608 | 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. |
| ID | Term |
|---|---|
| D016511 | Severe Combined Immunodeficiency |
| D015212 | Inflammatory Bowel Diseases |
| ID | Term |
|---|---|
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D049914 | DNA Repair-Deficiency Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| D014554 | Urination |
| ID | Term |
|---|---|
| D014553 | Urinary Tract Physiological Phenomena |
| D012101 | Reproductive and Urinary Physiological Phenomena |
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