Recruiting

Observational StudyEtiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia

Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Code:

NCT00867269

Conditions

Idiopathic CD4+ Lymphocytopenia

Cryptococcal Meningitis

Warts

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Study Details

Brief summary:

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.

Conditions

Idiopathic CD4+ Lymphocytopenia

Cryptococcal Meningitis

Warts

Study ID

NCT00867269

Start date

Jul 13, 2009

Status verified date

Jan 8, 2026

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

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 greater than or equal to 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.

Study Design

Enrollment

950 participants

Anticipated

Interventions and Outcome Measures

Arms

Blood Relatives

Blood Relatives of ICL subjects

Household Contacts

Household contacts of ICL subjects

ICL Subjects

Patients with confirmed idiopathic CD4 lymphocytopenia

Primary outcome measure

CD4 <300/microliters or < 20% of total T cells and their blood [ Time Frame: Baseline and annually ]

Central Contacts and Locations

Central contacts

Irini Sereti, M.D.

(301) 496-5533 isereti@niaid.nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

More Information

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Last update posted

Aug 31, 2026

Last verified

Jan 8, 2026

Keywords

Opportunistic Infection
Immunodeficiency Syndrome
Autoimmune Disease
CD4+ Lymphocytes
Natural History
Idiopathic CD4 Lymphocytopenia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Institute of Allergy and Infectious Diseases (NIAID) on 2026-08-31.