Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome (ACTION)
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|ClinicalTrials.gov Identifier: NCT03912129|
Recruitment Status : Not yet recruiting
First Posted : April 11, 2019
Last Update Posted : April 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Evans Syndrome||Genetic: blood sample||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome|
|Estimated Study Start Date :||May 6, 2019|
|Estimated Primary Completion Date :||May 6, 2022|
|Estimated Study Completion Date :||May 6, 2022|
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.
Genetic: 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.
- Number of patients for whom a causal mutation has been identified (known or new) [ Time Frame: after the genetic analyzes carried out on all the participants included, may 2022 ]
- The number of biological samples collected for PSE children included in the OBS'CEREVANCE cohort and their relatives will be recorded [ Time Frame: every 3 months, between may 2019 and may 2022 ]
- Immunopathological clinical manifestations [ Time Frame: after the genetic analyzes carried out on all the participants included, may 2022 ]
- Abnormalities of lymphocyte immunophenotyping [ Time Frame: 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 [ Time Frame: after the genetic analyzes carried out on all the participants included, may 2022 ]
- Physiopathological and potentially therapeutic classification of pES-T [ Time Frame: after the genetic analyzes carried out on all the participants included, may 2022 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03912129
|Contact: Nathalie Aladjidi, M.D||05 57 82 02 email@example.com|
|Contact: Aurore CAPELLI, PhD||05 57 82 08 firstname.lastname@example.org|