Genetic Basis of Immunodeficiency

The Determination of Genetic Basis Of Immunodeficiency

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.

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Study Overview

• Status: Recruiting
• Conditions: Severe Combined Immunodeficiency

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
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Warren J Leonard, M.D.; Phone Number: (301) 496-0098; Email: wl2w@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 98 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Primary clinical

Description

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify forms of inherited immunodeficiency resulting from mutation of yc dependent cytokines, components of their receptors, or signaling molecules in their pathways	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.	ongoing

Collaborators and Investigators

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

Publications and helpful links

General 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.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2004

Study Registration Dates

• First Submitted: February 20, 2003
• First Submitted That Met QC Criteria: February 19, 2003
• First Posted (Estimated): February 20, 2003

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: February 20, 2024

More Information

Terms related to this study

• Keywords: Natural History; Cytokines; Inherited Immunodeficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Severe Combined Immunodeficiency
• Other Study ID Numbers: 030105; 03-H-0105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No