Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Number of patients with chronic hepatic and/or digestive abnormalities
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- 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)
排除标准
- •Patients not belonging to one of the target populations
- •Opposition of legal representatives of minor patients, patients themselves and adult patients
结局指标
主要结局
Number of patients with chronic hepatic and/or digestive abnormalities
时间窗: 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
时间窗: 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
时间窗: Day 0
We will use the homogeneity test Chi-square to compare the distribution of enteric virus groups (EVAH and controls).
次要结局
- 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)
- Phenotypically characterize the cellular response in EVAH patients(Day 0)
- Transcriptionally characterize the cellular response in EVAH patients(Day 0)
- Specific anti-viral responses in patients presenting enteric virus associated hepatitis (EVAH)(Day 0)