Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 374
- 试验地点
- 1
- 主要终点
- The number of biological samples collected for PSE children included in the OBS'CEREVANCE cohort and their relatives will be recorded
研究概览
简要总结
Characterization of the genetic causes, and of the immunopathological clinical and biological manifestations in children with pediatric Evans syndrome included in a prospective national observational cohort of rare diseases.
详细描述
Pediatric Evans syndrome (pES) is a rare and severe disease combining immunologic thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). French patients from the 30 hematologic pediatric centers are from 2004 included in a prospective national OBS'CEREVANCE cohort.
A first pilot study revealed a monogenic cause in 7/18 patients (40%) with mutations in the CTLA-4, LRBA, STAT3 GOF, and KRAS. TNGS or exome studies were performed between 2015 and 2018 inn 80 patients with pSE from the OBS'CEREVANCE cohort. This approach, combined with by immunophenotyping lymphocyte, identified a genetic cause of the disease in 26 patients (32%) (TNFRSF6, CTLA4, LRBA, STAT3 GOF, PIK3CD, RAG1, KRAS) and potential causal mutations in 18 other patients (22%), bringing the proportion of potential single gene cause to 76%.
The central hypothesis of this study is that most, if not all, cases of pSE are related to a monogenic or digenic cause, possibly with the intervention of genetic modifiers such as somatic mutations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient registered in the French national prospective OBS'CEREVANCE cohort
- •Diagnosis of pediatric Evans syndrome (PTI+AHAI)
- •Age strictly under 18 years at the initial onset
- •Child residing in metropolitan France and affiliated to a french health insurance system
- •Free, informed, written and signed consent
排除标准
- •Evans syndrome secondary to chemotherapy, bone marrow transplantation or organ transplantation.
- •Refusal to participate from parents/patients
研究组 & 干预措施
pediatric Evans Syndrome
Collection of biological samples of children with pSE included in the the OBS'CEREVANCE cohort and their parents, for genetic and functional immunological analyzes.
干预措施: blood sample (Genetic)
结局指标
主要结局
The number of biological samples collected for PSE children included in the OBS'CEREVANCE cohort and their relatives will be recorded
时间窗: every 3 months, between may 2019 and may 2022
Number of patients for whom a causal mutation has been identified (known or new)
时间窗: after the genetic analyzes carried out on all the participants included, may 2022
次要结局
- Abnormalities of lymphocyte immunophenotyping(after the genetic analyzes carried out on all the participants included, may 2022)
- Physiopathological and potentially therapeutic classification of pES-T(after the genetic analyzes carried out on all the participants included, may 2022)
- Immunopathological clinical manifestations(after the genetic analyzes carried out on all the participants included, may 2022)
- The correlation between causal mutations identified with the clinical and immunological phenotype(after the genetic analyzes carried out on all the participants included, may 2022)