Clinical trial NCT03912129: Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome
Official title: Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Evans Syndrome
Keywords: pediatric Evans Syndrome
genetic causes
immunophenotyping immunologic explorations
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Institut des maladies génétiques, Paris
First posted: 2019-04-11
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients for whom a causal mutation has been identified (known or new)
timeFrame: after the genetic analyzes carried out on all the participants included, may 2022
measure: The number of biological samples collected for PSE children included in the OBS'CEREVANCE cohort and their relatives will be recorded
timeFrame: every 3 months, between may 2019 and may 2022
Secondary outcomes:
measure: Immunopathological clinical manifestations
timeFrame: after the genetic analyzes carried out on all the participants included, may 2022
measure: Abnormalities of lymphocyte immunophenotyping
timeFrame: after the genetic analyzes carried out on all the participants included, may 2022
measure: The correlation between causal mutations identified with the clinical and immunological phenotype
timeFrame: after the genetic analyzes carried out on all the participants included, may 2022
measure: Physiopathological and potentially therapeutic classification of pES-T
timeFrame: after the genetic analyzes carried out on all the participants included, may 2022
Other outcomes:
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