Severe PID With Lymphoproliferation and Neutropenia

Study Overview
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Brief Summary
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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

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

Conditions
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Primary Immune-Deficiency (PID) Common Variable Immune Deficiency (CVID)

Intervention / Treatment
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* Genetic: FACS analyses
* Genetic: Target Sequencing by NGS ( Next-generation sequencing)
* Genetic: Whole Exome Sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : >18 years old CVID (Common Variable Immunodeficiency) Neutropenia Lymphoproliferation Exclusion Criteria : - Secondary immunodeficiency

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of known mutations by target sequencing of all known genes involved in CVID phenotypes. | Target-NGS | Day 0 (inclusion) | 
| Identification of new mutations in new genes in CVID by WES (whole exome sequencing) strategy. | WES (Whole exome sequencing), If no known mutations is founded by T-NGS | Day 0 (inclusion) | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | After WES analyses | Day 0 (inclusion) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CVID, Neutropenia, Autoimmunity, Lymphoproliferation