DICEP: Severe PID With Lymphoproliferation and Neutropenia

Sponsor

University Hospital, Strasbourg, France (Other)

Overall Status

Completed

CT.gov ID

NCT03427593

Collaborator

(none)

Enrollment

Location

Arms

20.8

Actual Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to analyse the phenotype in a sub-population of adults with severe primary immunodeficiency with lymphoproliferation and neutropenia and to decipher the possible pathways involved, especially under the hypothesis of a CTLA4/LRBA schema

Condition or Disease	Intervention/Treatment	Phase
Primary Immune-Deficiency (PID) Common Variable Immune Deficiency (CVID)	Genetic: FACS analyses Genetic: Target Sequencing by NGS ( Next-generation sequencing) Genetic: Whole Exome Sequencing	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Phenotype-genotype Correlation in a Sub-population of Severe Primary Immunodeficiency With Lymphoproliferation and Neutropenia

Actual Study Start Date :

Mar 13, 2018

Actual Primary Completion Date :

Mar 13, 2018

Actual Study Completion Date :

Dec 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients Patients with the phenotype (PID and Neutropenia and lymphoproliferation)	Genetic: FACS analyses FACS analyses Genetic: Target Sequencing by NGS ( Next-generation sequencing) Target Sequencing by NGS ( Next-generation sequencing) Genetic: Whole Exome Sequencing Whole Exome Sequencing
Other: relatives (parents)	Genetic: FACS analyses FACS analyses Genetic: Target Sequencing by NGS ( Next-generation sequencing) Target Sequencing by NGS ( Next-generation sequencing) Genetic: Whole Exome Sequencing Whole Exome Sequencing
Sham Comparator: Controls	Genetic: FACS analyses FACS analyses

Arm

Intervention/Treatment

Experimental: Patients

Patients with the phenotype (PID and Neutropenia and lymphoproliferation)

Genetic: FACS analyses

FACS analyses

Genetic: Target Sequencing by NGS ( Next-generation sequencing)

Target Sequencing by NGS ( Next-generation sequencing)

Genetic: Whole Exome Sequencing

Whole Exome Sequencing

Other: relatives (parents)

Genetic: FACS analyses

FACS analyses

Genetic: Target Sequencing by NGS ( Next-generation sequencing)

Target Sequencing by NGS ( Next-generation sequencing)

Genetic: Whole Exome Sequencing

Whole Exome Sequencing

Sham Comparator: Controls

Genetic: FACS analyses

FACS analyses

Outcome Measures

Primary Outcome Measures

Identification of known mutations by target sequencing of all known genes involved in CVID phenotypes. [Day 0 (inclusion)]
Target-NGS
Identification of new mutations in new genes in CVID by WES (whole exome sequencing) strategy. [Day 0 (inclusion)]
WES (Whole exome sequencing), If no known mutations is founded by T-NGS
Validation or not of a pathological pathway involving CTLA4/LRBA or a related pathway in T-cells. Validation by the mean of functional analysis of T-cells in vitro of CTLA4 expression and response to stimulation. RNA-sequencing in sorted cells. [Day 0 (inclusion)]

Secondary Outcome Measures

Deciphering of new possible genes involved in the phenotype : Patient without known mutation in genes involved in PID will benefit of an extended analyse of the WES to find a possible condidate genes [Day 0 (inclusion)]
After WES analyses