Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome

Evans Syndrome Clinical Trial

— ACTION  

Official title:

Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03912129
• Other study ID #: CHUBX 2018/49
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 6, 2019
• Est. completion date: May 6, 2022

Study information

• Verified date: April 2019
• Source: University Hospital, Bordeaux
• Contact: Nathalie Aladjidi, M.D
• Phone: 05 57 82 02 79
• Email: nathalie.aladjidi[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: May 6, 2022
• Est. primary completion date: May 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Hemolytic, Autoimmune
• Evans Syndrome
• Syndrome
• Thrombocytopenia

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Institut des maladies génétiques, Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Secondary	Immunopathological clinical manifestations		after the genetic analyzes carried out on all the participants included, may 2022
Secondary	Abnormalities of lymphocyte immunophenotyping		after the genetic analyzes carried out on all the participants included, may 2022
Secondary	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
Secondary	Physiopathological and potentially therapeutic classification of pES-T		after the genetic analyzes carried out on all the participants included, may 2022