Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
| Status: | Recruiting |
|---|---|
| Conditions: | Infectious Disease, Hematology |
| Therapuetic Areas: | Hematology, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/17/2019 |
| Start Date: | March 19, 2009 |
| Contact: | Megan V Anderson, R.N. |
| Email: | megan.anderson2@nih.gov |
| Phone: | (301) 761-7323 |
Background:
- Idiopathic CD4+ lymphocytopenia (ICL) is a condition in which there is a decreased level
of CD4+ lymphocytes (a type of white blood cell), which can lead to opportunistic
infections or autoimmune disorders and diseases.
Objectives:
- To characterize the natural history with regard to CD4+ T cell count and onset of
infection, malignancy, and autoimmunity.
- To describe the immunological status of patients affected by ICL while providing the
best possible standard therapy to eradicate opportunistic infections.
- To establish the timeline of CD4 lymphocytopenia, with particular focus on defining
subgroups of patients according to the decline, stabilization, or rise of CD4+ T cell
counts over time.
- To characterize the opportunistic infections that occur in ICL patients at microbiologic
and molecular levels.
- To characterize the immunophenotype and possible genetic immunodeficiency causes of ICL.
- To determine whether measurable immunologic parameters correlate with the development of
opportunistic infections or other comorbidities such as lymphoma in patients with ICL.
- To determine whether there is any association between ICL and autoimmunity.
- To determine CD4+ T cell turnover, survival, functionality, and cytokine responsiveness
in ICL patients.
Eligibility:
- Patients 2 years of age and older with an absolute CD4 count less than 300 in children 6
years or older and adults or less than 20% of T cells in children younger than 6 on two
occasions at least 6 weeks apart.
- Patients with negative results of HIV testing by ELISA, Western Blot, and viral load.
- Patients must not have underlying immunodeficiency conditions, be receiving cytotoxic
chemotherapy (anti-cancer drugs that kill cells), or have cancer.
Design:
- At the initial visit to the National Institutes of Health, the following evaluations
will be conducted:
- Personal and family medical histories.
- Physical examination, including rheumatology evaluation and other consultations as
medically indicated (e.g., dermatology, pulmonology, ophthalmology, imaging studies).
- Blood samples for analysis of red and white blood cell counts, liver function, immune
hormones, and antibody and autoantibody levels, white blood cell growth and function,
and DNA.
- Urinalysis and urine pregnancy testing for female patients of childbearing age.
- Evaluation and treatment of active infections as medically indicated, including
biopsies, buccal swabs, pulmonary function tests, and imaging studies.
- Follow-up visits will take place approximately every 12 months or more frequently if
indicated, and will continue for a minimum of 4 years and a maximum of 10 years.
- Evaluations at follow-up will include blood samples (i.e., CBC with differential,
biochemical profile, HIV testing, etc.) and urinalysis and rheumatology consults.
- Idiopathic CD4+ lymphocytopenia (ICL) is a condition in which there is a decreased level
of CD4+ lymphocytes (a type of white blood cell), which can lead to opportunistic
infections or autoimmune disorders and diseases.
Objectives:
- To characterize the natural history with regard to CD4+ T cell count and onset of
infection, malignancy, and autoimmunity.
- To describe the immunological status of patients affected by ICL while providing the
best possible standard therapy to eradicate opportunistic infections.
- To establish the timeline of CD4 lymphocytopenia, with particular focus on defining
subgroups of patients according to the decline, stabilization, or rise of CD4+ T cell
counts over time.
- To characterize the opportunistic infections that occur in ICL patients at microbiologic
and molecular levels.
- To characterize the immunophenotype and possible genetic immunodeficiency causes of ICL.
- To determine whether measurable immunologic parameters correlate with the development of
opportunistic infections or other comorbidities such as lymphoma in patients with ICL.
- To determine whether there is any association between ICL and autoimmunity.
- To determine CD4+ T cell turnover, survival, functionality, and cytokine responsiveness
in ICL patients.
Eligibility:
- Patients 2 years of age and older with an absolute CD4 count less than 300 in children 6
years or older and adults or less than 20% of T cells in children younger than 6 on two
occasions at least 6 weeks apart.
- Patients with negative results of HIV testing by ELISA, Western Blot, and viral load.
- Patients must not have underlying immunodeficiency conditions, be receiving cytotoxic
chemotherapy (anti-cancer drugs that kill cells), or have cancer.
Design:
- At the initial visit to the National Institutes of Health, the following evaluations
will be conducted:
- Personal and family medical histories.
- Physical examination, including rheumatology evaluation and other consultations as
medically indicated (e.g., dermatology, pulmonology, ophthalmology, imaging studies).
- Blood samples for analysis of red and white blood cell counts, liver function, immune
hormones, and antibody and autoantibody levels, white blood cell growth and function,
and DNA.
- Urinalysis and urine pregnancy testing for female patients of childbearing age.
- Evaluation and treatment of active infections as medically indicated, including
biopsies, buccal swabs, pulmonary function tests, and imaging studies.
- Follow-up visits will take place approximately every 12 months or more frequently if
indicated, and will continue for a minimum of 4 years and a maximum of 10 years.
- Evaluations at follow-up will include blood samples (i.e., CBC with differential,
biochemical profile, HIV testing, etc.) and urinalysis and rheumatology consults.
Idiopathic CD4+ lymphocytopenia (ICL) is a disorder characterized by decreased numbers of
circulating CD4+ T lymphocytes in the absence of known causes of CD4+ lymphocytopenia. ICL is
defined as an absolute CD4+ T cell count of less than 300 cells/microL in a patient with no
human immunodeficiency virus infection or known immunodeficiency syndrome. The causes and
frequency of the disorder remain unknown. The condition is typically diagnosed when patients
present with a serious infection. In this natural history protocol, we will evaluate patients
with CD4+ T cell counts below 300 cells/microL. We propose to follow 200 ICL patients for a
minimum of 4 and maximum of 20 years, with a particular focus on the association between ICL
and autoimmune disease. In addition to the ICL patients, we will enroll blood relatives and
household contacts to better understand pathogenesis and etiologies of the syndrome. We will
collect blood and other tissues for immunologic, rheumatologic, and genetic testing in an
effort to identify and understand the underlying defects that cause ICL and follow its course
in a cohort of patients who will receive best standard therapy for opportunistic infections.
circulating CD4+ T lymphocytes in the absence of known causes of CD4+ lymphocytopenia. ICL is
defined as an absolute CD4+ T cell count of less than 300 cells/microL in a patient with no
human immunodeficiency virus infection or known immunodeficiency syndrome. The causes and
frequency of the disorder remain unknown. The condition is typically diagnosed when patients
present with a serious infection. In this natural history protocol, we will evaluate patients
with CD4+ T cell counts below 300 cells/microL. We propose to follow 200 ICL patients for a
minimum of 4 and maximum of 20 years, with a particular focus on the association between ICL
and autoimmune disease. In addition to the ICL patients, we will enroll blood relatives and
household contacts to better understand pathogenesis and etiologies of the syndrome. We will
collect blood and other tissues for immunologic, rheumatologic, and genetic testing in an
effort to identify and understand the underlying defects that cause ICL and follow its course
in a cohort of patients who will receive best standard therapy for opportunistic infections.
- ICL PARTICPANT INCLUSION CRITERIA:
To be eligible for this study, patients must satisfy all of the following inclusion
criteria:
1. Age greater than or equal to 18 years
2. Absolute CD4 count < 300 cells/microL or < 20% of total T cells on at least two
occasions at least 6 weeks apart
3. Ongoing care by a referring primary care physician
4. Willingness to allow storage of blood and tissue samples for future analysis
ICL PARTICPANT EXCLUSION CRITERIA:
Patients will be ineligible for this study if they satisfy any of the following criteria:
1. Known infection with HIV-1, HIV-2, or human T-cell lymphotropic viruses (HTLV-1 or
HTLV-2) as demonstrated by enzyme-linked immunosorbent assay (ELISA) and western blot
and/or viral load testing
2. Known underlying immunodeficiency syndrome other than ICL
3. Evidence of active malignancy
4. Receipt of medications, herbal substances, or biologic agents known to diminish the
CD4+ count within 30 days of when the CD4+ lymphocytopenia was detected
5. Any condition that in the judgment of the investigators would place the subject at
undue risk or compromise the results of the study.
BLOOD RELATIVE INCLUSION CRITERIA:
To be eligible for study participation as a blood relative, subjects must be (Bullet)18
years of age and be a blood relative of an individual who meets or has met the CDC criteria
for ICL.
HOUSEHOLD CONTACT INCLUSION CRITERIA:
To be eligible for study participation as a household contact, subjects must be greater
than or equal to18 years of age and live within the same household as an ICL subjects
participating in this protocol. Blood relatives who are household contacts are eligible to
participate.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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