Consequences of DNA Repair and Telomere Defects on the Function of the Immune System: Application to CVID and Immune Deficiencies With Dysmorphic Syndromes

• Conditions: Immune Deficiency and Early BMF in Childhood

• Registration Number: NCT02556359
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The molecular mechanisms participating in the various aspects of the DNA Damage Response (DDR) are absolutely essential to maintain the genome dynamics essential to all living organisms. The most commonly studied consequence of faulty DDR is genome instability participating in cancer onset. In the present proposal, we wish to explore another aspect of DDR, not relevant to cancer, which is its absolute requirement at several key steps of the development, maturation, and function of the immune system.

The most "spectacular" consequences of faulty DNA repair processes with respect to the immuno-hematopoietic tissue are the complete block of B and T lymphocytes maturation owing to defective DNA joining phase during V(D)J recombination resulting in patients with Severe Combined Immune Deficiency (SCID).

The objectives of this study are to increase our knowledge on the role of the various DNA repair processes in the development, the maintenance, and the function of the immune system and thus, to better understand why and how dysfunctions of these DNA repair processes result in human severe conditions such as CVID, LOCID or other manifestations of immune disorders such as autoimmunity.

The explorations of DNA repair mechanisms in the patients will allow us to establish the genetic diagnosis in some patients with until now undefined molecular diagnosis. This is of immediate importance for the patients and their families, as it not only contributes to a better understanding of the patients' condition, but also allows providing genetic counseling for the families.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2015-09-21
• Study First Submitted QC: 2015-09-21
• Study First Posted: 2015-09-22
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-15
• Last Update Posted: 2016-04-18
• Primary Completion: 2019-07
• Study Completion: 2019-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Immune Deficiency and early BMF in childhood
• Common Variable Immunodeficiency (CVID)
• Genetic patients

Exclusion Criteria

• Refusal to consent.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
DNA abnormailities	1 day

Trial Locations

Locations (1)

Saint Louis hospital; 🇫🇷 Paris, France