This protocol is being submitted to consolidate, update, and expand two previously approved
protocols (77-C-0066 and 82-C-0044) into a single protocol. The purpose of this study is to
examine the factors involved in the regulation of the immune system of healthy individuals
and to define the abnormalities in this regulation that underlies the immunological disorders
of patients with a variety of immunodeficiency and malignant disorders. The studies will
include the ex vivo phenotypic and functional analysis of the network of cells involved in
humoral and cellular immune responses, and in vivo testing for the capacity to make
delayed-type hypersensitivity and humoral responses following immunization with a variety of
antigens. Individuals to be studied will include patients with a variety of malignancies and
patients with primary and secondary immunodeficiency disorders. Selected family members or
family members known to be genetic carriers of certain immunodeficiency diseases as well as
normal, unrelated individuals will also be studied. A small number of procedures will be used
including analysis of blood obtained by phlebotomy, apheresis, skin testing and recall
antigens and immunization to assess humoral immunity.
- The evaluation of the cells of the immune system and HTLV-1 infection have been a
central focus of the Metabolism Branch for the past 30 years.
- Blood obtained by apheresis or blood drawing, skin biopsies and other tissues will be
evaluated for abnormalities related to immunity, HTLV-1 infection and the immune system.
- Advances in the characterization of acquired genetic changes in tumor samples has
led to insights for the development of targeted therapy of malignancy
- To characterize the molecular biology and immunological features as well as the clinical
course of individuals with suspected or known disorders of the immune system or cancer.
- To define the nature of the immunological, genetic and epigenetic abnormalities in the
cells of patients with immunodeficiency diseases associated with infections and/or a
high incidence of malignancy and in patients with cancer.
- To obtain whole blood, plasma, and leukocytes, as well as skin, lymph node and bone
marrow biopsies on patients with immunodeficiency or cancer to investigate the immune
- Subjects with cancer.
- Subjects with immunodeficiency.
- Subjects with HTLV-1 infection.
-This is a natural history study that permits tissue acquisition for analysis of the immune
system and HTLV-1 infection.
- INCLUSION CRITERIA:
Patient must meet at least one of these criteria:
Have suspected or known disorder of the immune system or cancer
Be a known or potential carrier of autoimmune disorder or immunodeficiency disease.
Specific disorders may include but are not limited to:
- X-linked (severe combined immunodeficiency)
- Autosomal recessive SCID
- X-linked CD40 ligand deficiency
- Common variable immunodeficiency
- Wiskott Aldrich syndrome
- DiGeorge syndrome
- Infection with HTLV-1
Age of birth and above for patients with suspected or known disorders of the immune system
Patient (or parent/guardian of a minor child) must be able to understand and sign informed
Patients who will undergo apheresis must have hematocrit greater than 28%, and platelet
count greater than 50,000.
Subjects for whom apheresis is desired but whose counts are lower than those above must be
evaluated and approved by a Department of Transfusion Medicine consult physician.
Weight greater than 25 kg is necessary for apheresis.
Overall Exclusion Criteria:
Pregnant women will not be eligible for any aspect of this protocol
Children less than 18 years old are not eligible for lymph node or bone marrow biopsy
Exclusion Criteria for skin/parenteral antigen tests:
Any history of severe reaction or allergy to a particular skin test antigen or other
ingredients in the formulation (e.g. Thimerosal, eggs or avian protein) will exclude a
subject from receiving that particular skin test.
Children under the age of 2 years are not eligible to receive the Pneumococcal polyvalent
Subjects under the age of 18 years are not eligible to receive the Candida skin test
Exclusion Criteria for Apheresis Alone:
Any diagnosed medical condition which may be worsened by the apheresis procedure.
Specifically the patient should not have any of the following:
1. Congestive Heart Failure
2. History of angina
3. Severe hypotension (at the discretion of the patient's physician, the apheresis staff
and the attending physician from the Department of Transfusion Medicine (DTM) per DTM
Standard Operating Policies.)
4. Poorly controlled hypertension (average baseline blood pressure greater than 160/90)
5. History of a coagulation protein disorder.
Pediatric patients (less than 18 years) will not undergo apheresis.