Overview
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.
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
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