Genetic Basis of Immunodeficiency

• ClinicalTrials.gov Identifier: NCT00055172
• Recruitment Status: Recruiting
• First Posted: February 20, 2003
• Last Update Posted: May 16, 2024
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Tracking Information

• First Submitted Date: February 20, 2003
• First Posted Date: February 20, 2003
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: April 5, 2004
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: May 11, 2019)

To identify forms of inherited immunodeficiency resulting from mutation of yc dependent cytokines, components of their receptors, or signaling molecules in their pathways [ Time Frame: ongoing ]

In an effort to determine the cause of the immunodeficiency, we will perform studies that may include but not be limited to evaluating the levels of expression of protein and/or mRNA, obtaining DNA sequence data, performing epigenetic studies, and evaluating biological function using cellular, biochemical, or other molecular studies.

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Genetic Basis of Immunodeficiency
• Official Title: The Determination of Genetic Basis Of Immunodeficiency

Brief Summary

This study will examine the role of hereditary factors in different forms of severe combined immunodeficiency (SCID).

Patients with immunodeficiencies may be eligible for this study. Candidates include:

• Patients with diminished numbers of T cells or NK cells or both, or
• Patients with normal T cell and NK cell numbers but diminished T cell, B cell, or NK cell function.

Relatives of patients will also be studied.

Participants will have blood samples collected for genetic analysis in studies related to SCID at the National Institutes of Health and other institutions.

...

• Detailed Description: The goal of this project is to identify the genetic basis of new forms of inherited immunodeficiency. The particular focus relates to cytokines such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 that share the common cytokine receptor (Gamma) chain, (Gamma c), and to molecules that are important for signaling or gene regulation in response to these cytokines, although other causes of inherited immunodeficiency are also encompassed.
• Study Type: Observational
• Study Design: Observational Model: Family-Based; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Primary clinical
• Condition: Severe Combined Immunodeficiency
• Intervention: Not Provided

Study Groups/Cohorts

• Non-sibling relative
  18 years of age or older
• Patients (index cases)
  Patients (index cases), 6 months of age or older
• Siblings
  Siblings, 6 months of age or older

Publications *

• Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 1993 Apr 9;73(1):147-57. doi: 10.1016/0092-8674(93)90167-o.
• Russell SM, Tayebi N, Nakajima H, Riedy MC, Roberts JL, Aman MJ, Migone TS, Noguchi M, Markert ML, Buckley RH, O'Shea JJ, Leonard WJ. Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science. 1995 Nov 3;270(5237):797-800. doi: 10.1126/science.270.5237.797.
• Puel A, Ziegler SF, Buckley RH, Leonard WJ. Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. Nat Genet. 1998 Dec;20(4):394-7. doi: 10.1038/3877.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 1, 2021): 100
• Original Enrollment (submitted: June 23, 2005): 999999
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility Criteria

• INCLUSION CRITERIA:

Index cases to be included are those with diminished numbers of T cells and/or NK cells and/or B cells or other immune cells or those who have normal numbers of T cell, B cells, NK cells and other immune cells but diminished function of one or more immune cells. Relatives of affected individuals may also be studied

• Patients (index cases): 6 months of age and older
• Siblings: 6 months of age and older
• Non-sibling relatives (biological parent, aunt, uncle or grandparent): 18 years or older

EXCLUSION CRITERIA:

• Patients with a known diagnosis
• Patients with a particular immunological phenotype that is not of interest to the research conducted under this study.
• Pregnancy or lactation
• Adults with current decisional impairment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 99 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Warren J Leonard, M.D.; (301) 496-0098; wl2w@nih.gov

• Listed Location Countries: United States
• Removed Location Countries: Chile

Administrative Information

• NCT Number: NCT00055172
• Other Study ID Numbers: 030105; 03-H-0105
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Warren J Leonard, M.D.; National Heart, Lung, and Blood Institute (NHLBI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: February 20, 2024