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

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.

Study Overview

• Status: Unknown
• Conditions: Immune Deficiency and Early BMF in Childhood

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Saint Louis Hospital
    • Contact: Claire Fieschi, MD PhD; Phone Number: +33 1 42 49 45 83; Email: claire.fieschi@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Any patient presenting clinical immune deficiency and at least one associated feature hinting at a possible DNA repair defect, such as microcephaly, growth retardation starting in utero, distinctive facial appearance ("bird-like face"), developmental delay, cerebellar degeneration, UV light sensitivity, premature aging, dystrophic nails, dental abnormalities, hair anomalies, pancytopenia and/or bone marrow failure

Description

Inclusion Criteria:

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

Exclusion Criteria:

• Refusal to consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
DNA abnormailities	1 day

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimate): September 22, 2015

Study Record Updates

• Last Update Posted (Estimate): April 18, 2016
• Last Update Submitted That Met QC Criteria: April 15, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes
• Other Study ID Numbers: RTC13005