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.

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 in response to these cytokines.

• 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.
• Russell SM, Tayebi N, Nakajima H, Riedy MC, Roberts JL, Aman MJ, Migone TS, Noguchi M, Markert ML, Buckley RH, et al. Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science. 1995 Nov 3;270(5237):797-800.
• 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.

• INCLUSION CRITERIA:

Patients to be included are those with diminished numbers of T cells and/or NK cells or those who have normal T cell and NK cell numbers but diminished T cell, B cell, or NK cell function. 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 to be excluded are those with a known diagnosis or those who are related to an individual with an immunodeficiency of known cause. Other patients may be excluded based on the particular immunological phenotype or the inability of the laboratory to handle additional cases at a given time