Genetic Basis of Immunodeficiency

• ClinicalTrials.gov Identifier: NCT00055172
• Recruitment Status: Recruiting
• First Posted: February 20, 2003
• Last Update Posted: May 8, 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) )

Study Description

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.

...

Condition or disease
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 Design

• Study Type: Observational
• Estimated Enrollment: 100 participants
• Observational Model: Family-Based
• Time Perspective: Cross-Sectional
• Official Title: The Determination of Genetic Basis Of Immunodeficiency
• Actual Study Start Date: April 5, 2004

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 99 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Primary clinical

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

Contacts and Locations

Contacts

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

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY dial 711 ccopr@nih.gov

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

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

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

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.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT00055172
• Other Study ID Numbers: 030105; 03-H-0105
• First Posted: February 20, 2003
• Last Update Posted: May 8, 2024
• Last Verified: February 20, 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):

Cytokines; Inherited Immunodeficiency; Natural History

Additional relevant MeSH terms:

Severe Combined Immunodeficiency; Immunologic Deficiency Syndromes; Immune System Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases