Molecular and Clinical Studies of Primary Immunodeficiency Diseases

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Brief Title

Molecular and Clinical Studies of Primary Immunodeficiency Diseases

Official Title

Molecular and Clinical Studies of Primary Immunodeficiency Diseases

Brief Summary

      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. Participants
      will undergo a medical and family history, physical examination, and additional procedures
      and tests that may include the following:

        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
           light sedation.

       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.

Detailed Description

      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.

Study Type


Primary Outcome

To broaden our current knowledge of the molecular basis, clinical presentation, evolution and outcome of primary immunodeficiencydiseases.


Wiskott- Aldrich Syndrome

Study Arms / Comparison Groups

 ADA deficient SCID
Description:  Patients with ADA deficient SCID


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

October 25, 2000

Eligibility 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
        the study.

        Patients who were enrolled under such inclusion criteria may continue to be seen under the
        protocol under the medical advisory supervision of Dr. Harry Malech. New enrollments will
        be limited to children with established and verified diagnosis of ADA-SCID cared for by our
        collaborators at UCLA and from whom we will only

        receive blood samples.


        Inability of the subject or the subject s parent/guardian to provide informed consent.

        Patients infected with the Human Immunodeficiency Virus before enrollment.




3 Years - N/A

Accepts Healthy Volunteers



Elizabeth K Garabedian, R.N., , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

National Human Genome Research Institute (NHGRI)

Study Sponsor

Elizabeth K Garabedian, R.N., Principal Investigator, National Human Genome Research Institute (NHGRI)

Verification Date

September 23, 2022