This study will try to identify mutations in the genes responsible for primary
immunodeficiency disorders (inherited diseases of the immune system) and evaluate the course
of these diseases in patients over time to learn more about the medical problems they cause.
The immune system is composed of various cells (e.g., T and B cells and phagocytes) and other
substances (complement system) that protect the body from infections and cancer.
Abnormalities in the gene(s) responsible for the function of these components can lead to
serious infections and other immune problems.
Patients with Wiskott-Aldrich syndrome, adenosine deaminase (ADA) deficiency, Janus
Associated Kinase 3 (JAK3) deficiency, common variable immunodeficiency (CVID) and other
immunodeficiencies may be eligible for this study. Participants will undergo a medical and
family history, physical examination, and additional procedures and tests that may include
1. Blood tests for: routine laboratory studies (i.e. cell counts, enzyme levels,
electrolytes, etc.); HIV testing; immune response to various substances; genetic
testing; and establishment of cell lines to maintain a supply of cells for continued
2. Urine and saliva tests for biochemical studies
3. Skin tests to assess response to antigens such as the viruses and bacteria responsible
for tetanus, candida, tuberculosis, diphtheria, chicken pox, and other diseases.
4. Skin and lymph node biopsies for tissue and DNA studies
5. Chest X-ray, CT scans, or both to look for cancer or various infections.
6. Pulmonary function test to assess lung capacity and a breath test to test for H. pylori
7. Dental, skin and eye examinations.
8. Treatment with intravenous immunoglobulins or antibodies to prevent infections.
9. Apheresis for collecting white blood cells to study cell function. In this procedure,
whole blood is collected through a needle placed in an arm vein. The blood circulates
through a machine that separates it into its components. The white cells are then
removed, and the red cells, platelets and plasma are returned to the body, either
through the same needle or through a second needle placed in the other arm.
10. Bone marrow sampling to study the disease. A small amount of marrow from the hipbone is
drawn (aspirated) through a needle. The procedure can be done under local anesthesia or
11. Placental and umbilical cord blood studies, if cord blood is available, to study stem
cells (cells that form blood cells).
Information gained from this study may provide a better understanding of primary
immunodeficiencies, leading to better diagnosis and treatment. In addition, study
participants may receive medical and genetic counseling and may be found eligible for other
NIH studies on these diseases.
The purpose of this protocol is to study patients with primary immunodeficiency disorders
with the goal of contributing to both the clinical and molecular understanding of this
heterogeneous group of inherited diseases. Clinical issues to be addressed will include
disease manifestations and evolution, as well prevention and management of medical problems.
Patients with diseases of known molecular basis (including Wiskott-Aldrich syndrome, ADA
deficiency, JAK3 deficiency and other syndromes) will be genotyped in order to investigate
phenotype-genotype correlation. Patients with disease of unknown or incomplete genetic
characterization will be studied with hopes of contributing to the identification of specific
genes responsible for disease. Studies of fresh cells, cell lines and tissue samples will be
performed to help characterize the patient s syndrome as well as to test the efficacy of
genetic correction when available.
The outcome we seek is to improve our knowledge of the molecular basis, clinical presentation
and evolution of primary immunodeficiency diseases and to collaborate to maintain or improve
the health status of our patients. No investigational clinical interventions are planned
under this protocol. It is anticipated that additional protocols will be generated from
preliminary data gathered in this umbrella study.
- INCLUSION CRITERIA:
Patients with a clinical history or signs and symptoms suggestive of a primary immune
deficiency syndrome and their family members are eligible for inclusion in this study and
they may be referred by their physician or self-referred. If possible, a local
physician/clinical immunologist will be identified for self-referred patients to serve as
primary reference. If screening of the patients, either by phone interview or review of
their medical records indicates that the patient may have a primary immunodeficiency
syndrome and is HIV-negative, the patient will be invited to come to the NIH and sign an
informed consent. If family history is positive for immunodeficiency, the patients or
family members may be asked to invite other relatives to contact the PI to participate in
Adult patient who are unable to provide informed consent are eligible to participate with
permission obtained from their legal guardian or durable power of attorney.
Inability of the subject or the subject s parent/guardian to provide informed consent.
Patients infected with the Human Immunodeficiency Virus before enrollment.