The Mechanistic Biology of Primary Immunodeficiency Disorders


Background: Primary immunodeficiency disorders, or PIDs, are diseases that weaken the immune system. This makes it easier for a person to get sick. Some PIDs are mild and may not be diagnosed until later in life. Other kinds are severe and can be identified shortly after birth. Researchers want to learn more about PIDs by comparing data from relatives and healthy volunteers to people with a PID. Objective: To learn more about PIDs, including their genetic causes. Eligibility: People ages 0 75 with a PID or their healthy biological relatives the same ages Healthy volunteers ages 18 75 Design: Participants will be screened with a medical history, physical exam, and HIV blood test. They may have a pregnancy test. Participants may repeat the screening tests. Blood taken at screening will be used for genetic tests and research tests. Participants will be told test results that affect their health. Some blood will be stored for future research. Adult participants with a PID may have a small piece of skin removed. The area will be numbed. A small tool will take a piece of skin about the size of a pencil eraser. Researchers may collect fluid or tissue samples from PID participants regular medical care. They will use them for research tests. Participants with a PID will have 3 follow-up visits over 10 years (for infants, 2 years). Visits will include a physical exam, medical history, and blood draw. Participants with a PID and their relatives will be called once a year for 10 years. They will talk about how they are feeling and if they have developed any new symptoms or illnesses. ...


  • Primary Immunodeficiency Disorders


Eligible Ages
Under 75 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  1. Subjects must meet one of the following 4 criteria:
  2. 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.
  3. 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.
  4. Biological relatives (age 0-75 years) of a subject who meets criterion 1a or 1b but who do not have a PID themselves.Relatives may be mother, father, siblings, children, grandparents, aunts, uncles, and first cousins to a patient. There is no limit due to sex,

race or disability. Women of child-bearing potential, or who are pregnant or lactating, may be eligible, however the volume of blood collected for research purposes will be reduced in consideration of their safety. Relatives must also be willing to undergo genetic


4. Healthy volunteers (age 18-75 years) who are not related to another study subject, who do not have a PID, and meet the folllowing:

- 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

- Not infected with HIV

- Not to be pregnant

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.

Study Design

Study Type
Observational Model
Time Perspective

Arm Groups

ArmDescriptionAssigned Intervention
1 Affected Patient
2 Relative of Patient
3 Normal Volunteer

Recruiting Locations

Children's National and nearby locations

Division of Allergy & Immunology Children's Hospital (CNHS)
Washington, District of Columbia 20010
Michael Keller, M.D.

More Details

National Institute of Allergy and Infectious Diseases (NIAID)

Study Contact

Luigi D Notarangelo, M.D.
(301) 761-7550

Detailed Description

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.