The Mechanistic Biology of Primary Immunodeficiency Disorders

This is a natural history study designed to investigate forms of primary immunodeficiency
disorders (PIDs), and to better define both new and previously described forms of PID,
including severe combined immunodeficiency (SCID), combined immunodeficiency, natural killer
(NK) cell deficiency, and other disorders. Patients with clinical and/or laboratory evidence
of PID will be recruited at Children s National Health System (CNHS) and the National
Institute of Allergy and Infectious Diseases (NIAID). Infants identified at birth with a
positive newborn screening for SCID and confirmed to have T-cell lymphocytopenia will also be
recruited at CNHS. Subjects with a known or unknown PID and infants with T-cell
lymphocytopenia will provide one or more blood donations during the course of the study to
enable immunologic and genetic investigations of immune pathways contributing to PIDs. These
subjects will also be followed clinically to longitudinally assess the natural history of
novel and known PIDs. Subjects will be followed over time with regard to their immunologic
phenotype, clinical disease (including incidence of infections, autoimmune phenomena,
allergic disease, or malignancies), and response to both preventative and definitive
therapies. Biological relatives who do not have PID and healthy adult volunteers will also be
eligible to serve as controls for this study.

- INCLUSION CRITERIA:

1. Subjects must meet one of the following 4 criteria:

1. Patients (age 0-75 years) with a clinical diagnosis of a form of PID (either
known or unknown). PID is defined by laboratory and/or clinical findings on
two or more occasions that are consistent with a defect in innate or
adaptive immunity. Specific PIDs are defined by the International Union of
Immunological Societies guidelines. These subjects must also be willing to
undergo genetic testing and to allow their biospecimens to be modified into
iPS cells. Women of childbearing potential, or who are pregnant or
lactating, may be eligible. The volume of blood collected for research
purposes will be reduced, and no skin biopsies will be performed for
research purposes in consideration of their safety.

2. Infants identified at birth with positive newborn screening for SCID and
confirmed to have T-cell lymphocytopenia. These subjects must be willing to
undergo genetic testing.

3. Biological relatives (age 0-75 years) of a subject who meets criterion 1a or
1b but who do not have a PID themselves. All relatives must be willing to
undergo genetic testing. Women of childbearing potential, or who are
pregnant or lactating, may be eligible. The volume of blood collected for
research purposes will be reduced in consideration of their safety.

4. Healthy volunteers (age 18-75 years) who are not related to another study
subject, who do not have a PID, whose weight is greater than 110 pounds, do
not have a history of any heart, lung, or kidney disease, or bleeding
disorders, do not have a history of viral hepatitis (B or C), and have a
negative HIV screening test.

2. All subjects must be willing to allow their samples to be stored for future
research.

EXCLUSION CRITERIA:

1. Subjects with secondary causes of immunodeficiency are excluded from this study.
Secondary causes of immunodeficiency include HIV infection and immunodeficiency that
is deemed to be secondary to chronic use of immunosuppressive medications or
chemotherapeutic agents.

2. Any condition that, in the opinion of the investigator, contraindicates participation
in this study.