Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome

Not Applicable

• Conditions: Evans Syndrome
• Interventions: Genetic: blood sample

• Registration Number: NCT03912129
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2019-04
• Study First Submitted: 2019-04-09
• Study First Submitted QC: 2019-04-09
• Last Update Submitted: 2019-04-09
• Study First Posted: 2019-04-11
• Last Update Posted: 2019-04-11
• Study Start: 2019-05-06
• Primary Completion: 2022-05-06
• Study Completion: 2022-05-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• 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

Exclusion Criteria

• Evans syndrome secondary to chemotherapy, bone marrow transplantation or organ transplantation.
• Refusal to participate from parents/patients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
pediatric Evans Syndrome	blood sample	Collection of biological samples of children with pSE included in the the OBS'CEREVANCE cohort and their parents, for genetic and functional immunological analyzes.

Primary Outcome Measures

Name	Time	Method
The number of biological samples collected for PSE children included in the OBS'CEREVANCE cohort and their relatives will be recorded	every 3 months, between may 2019 and may 2022
Number of patients for whom a causal mutation has been identified (known or new)	after the genetic analyzes carried out on all the participants included, may 2022

Secondary Outcome Measures

Name	Time	Method
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
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
Immunopathological clinical manifestations	after the genetic analyzes carried out on all the participants included, may 2022