Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome

NCT ID: NCT03912129

Last Updated: 2019-04-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-06

Study Completion Date

2022-05-06

Brief Summary

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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

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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.

Conditions

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Evans Syndrome

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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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.

Group Type OTHER

blood sample

Intervention Type GENETIC

A first systematic approach by Targeted-Next Generation Sequencing will be used on the entire cohort of patients with pSE. This step will be performed on a sequencing chip specifically developed to detect anomalies in known genes involved in autoimmunity.

In patients for whom no mutations are identified, a whole exome sequencing (WES) approach will be applied to patients and their parents to seek to identify mutations in new genes that may be related to pSE.

In patients for whom this WES approach is unsuccessful, the search for somatic lymphocyte mutations, or copy number variants will be performed before considering a complete genome sequencing .

If several candidate genes are identified, the clinical data provided by the CEREVANCE and the phenotypic analyses carried out prior to genetic analyses by the CEDI laboratory will guide the choices to prioritize the study of the identified variants.

Interventions

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blood sample

A first systematic approach by Targeted-Next Generation Sequencing will be used on the entire cohort of patients with pSE. This step will be performed on a sequencing chip specifically developed to detect anomalies in known genes involved in autoimmunity.

In patients for whom no mutations are identified, a whole exome sequencing (WES) approach will be applied to patients and their parents to seek to identify mutations in new genes that may be related to pSE.

In patients for whom this WES approach is unsuccessful, the search for somatic lymphocyte mutations, or copy number variants will be performed before considering a complete genome sequencing .

If several candidate genes are identified, the clinical data provided by the CEREVANCE and the phenotypic analyses carried out prior to genetic analyses by the CEDI laboratory will guide the choices to prioritize the study of the identified variants.

Intervention Type GENETIC

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut des maladies génétiques, Paris

UNKNOWN

Sponsor Role collaborator

University Hospital, Bordeaux

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Central Contacts

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Nathalie Aladjidi, M.D

Role: CONTACT

05 57 82 02 79

Aurore CAPELLI, PhD

Role: CONTACT

05 57 82 08 77

Other Identifiers

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CHUBX 2018/49

Identifier Type: -

Identifier Source: org_study_id

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