This study will evaluate HIV-negative patients with unusually low levels of CD4+ T
lymphocytes (a type of white blood cell) to learn more about the clinical symptoms, cause,
immunology, and biology of this problem. CD4+ T lymphocytes play an important role in immune
function, and low counts may leave people susceptible to unusual infections. CD4+ T cell
deficiencies are most often associated with HIV infection.
Patients 8 years of age and older with CD4+ T cell counts below 300 cells/mm3 who test
negative for HIV infection by standard blood tests may be eligible for this study. Patients'
family members and partners may also be enrolled to investigate the possible role of a
genetic factor or exposure to some agent in this problem.
Patients will be evaluated at the NIH Clinical Center at least once, and generally two or
more times. The evaluations, which may be done on an inpatient or outpatient basis, will
include some or all of the following tests and procedures:
- Complete physical examination.
- Medical history, including questions about sexual contacts, intravenous drug use,
travel, blood transfusions, previous illnesses, including sexually transmitted
diseases, and health of family members.
- Urine test.
- Blood tests for routine and research purposes, including tests for HIV, hepatitis,
syphilis and other infections, evaluation of immune function, and culture for viruses
in the HIV family. No more than 1 pint of blood will be drawn every 6 weeks.
- Pregnancy test for women of childbearing potential.
- Skin tests for tuberculosis and immune function. These tests involve injecting a small
amount of the substance to be tested just under the skin and looking for a raised area
1 to 2 days later.
- Apheresis. Whole blood is collected through an arm vein (similar to donating blood),
and circulated through a cell separator machine, where it is spun to separate the
components. The red cells are then returned to the patient either through the same
needle or through a needle in the other arm, and the plasma and white cells are
extracted for study. The procedure, which takes 1 to 2 hours, may be repeated up to 3
Family members will have 60 cc (4 tablespoons) of blood drawn to determine CD4+ T cell
Low CD4+ T-cells in the absence of known etiology has been called idiopathic CD4+ T
lymphocytopenia, and a case definition was established by the CDC as a CD4 count less than
300 cells/mL on 2 consecutive samples in a patient uninfected by HIV and with no other
disease or treatment that might provide a reasonable alternative explanation for CD4
lymphocytopenia. Early investigations centered on a search for a novel retrovirus, but we
and others have not found evidence of such a retrovirus. The patients that we have seen are
heterogeneous, and it appears likely that there will be multiple etiologies for this
syndrome. We are currently continuing to follow subjects long term and to see new subjects
in order to continue to characterize the clinical aspects of patients who meet the case
definition; to determine the natural history of ICL, and to provide samples to researchers
who are interested in investigations into the pathogenesis of ICL.
Adults greater than or equal to 18 years of age.
CD4 count less than 300 cells/mmL on 2 consecutive samples.
Uninfected by HIV as determined by ELISA with confirmatory Western Blot
Absence of disease or treatment that might provide a reasonable alternative explanation
for the CD4 cell count or might confound the evaluation. Examples of such diseases would
be any acute, severe medical illness that had not resolved when CD4 cell counts were
obtained; active tuberculosis; leukemia or lymphoma; or previously characterized
immunodeficiency disorder. Treatment that that might provide a reasonable alternative
explanation includes chemotherapy over a field that could affect bone marrow or
supraphysiologic glucocorticoid therapy.
Capable of providing informed consent.