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Protocol Details

Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required


Population Exclusion(s)


Special Instructions

Currently Not Provided


Idiopathic Lymphocytopenia;
Opportunistic Infection;
Immunodeficiency Syndrome;
Autoimmune Disease;
CD4+ Lymphocytes

Recruitment Keyword(s)

Idiopathic CD4 Lymphocytopenia


Idiopathic CD4+ lymphocytopenia;
Cryptococcal Meningitis;

Investigational Drug(s)


Investigational Device(s)




Supporting Site

National Institute of Allergy and Infectious Diseases


- 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.


- 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.


- 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.


- 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.

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To be eligible for this study, patients must satisfy all of the following inclusion criteria:

- Age greater than or equal to 18 years

- Absolute CD4 count < 300 cells/microL or < 20% of total T cells on at least two occasions at least 6 weeks apart

- Ongoing care by a referring primary care physician

- Willingness to allow storage of blood and tissue samples for future analysis


Patients will be ineligible for this study if they satisfy any of the following criteria:

- Known infection with HIV-1, HIV-2, or human T-cell lymphotropic viruses (HTLV-1 or HTLV-2) as demonstrated by ELISA and Western blot and/or viral load testing

- Known underlying immunodeficiency syndrome other than ICL

- Evidence of active malignancy

- Receipt of medications, herbal substances, or biologic agents known to diminish the CD4+ count within 30 days of when the CD4+ lymphocytopenia was detected

- Any condition that in the judgment of the investigators would place the subject at undue risk or compromise the results of the study.

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Fauci AS. CD4+ T-lymphocytopenia without HIV infection--no lights, no camera, just facts. N Engl J Med. 1993 Feb 11;328(6):429-31.

Laurence J, Siegal FP, Schattner E, Gelman IH, Morse S. Acquired immunodeficiency without evidence of infection with human immunodeficiency virus types 1 and 2. Lancet. 1992 Aug 1;340(8814):273-4.

Ho DD, Cao Y, Zhu T, Farthing C, Wang N, Gu G, Schooley RT, Daar ES. Idiopathic CD4+ T-lymphocytopenia--immunodeficiency without evidence of HIV infection. N Engl J Med. 1993 Feb 11;328(6):380-5.

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Principal Investigator

Referral Contact

For more information:

Virginia M. Sheikh, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
BG 10 RM 8C408
(301) 435-7939

Gregg A. Roby, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 8C312
10 Center Drive
Bethesda, Maryland 20892
(301) 435-8008
Email: Not Specified

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Clinical Trials Number:


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