NCT00867269

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

Recruiting now Last updated 14 April 2026

What this trial tests

trial in Idiopathic CD4+ Lymphocytopenia in 950 participants. Currently enrolling.

Timeline

13 July 2009

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	950
Start date	13 July 2009
Sites	1 location across United States

Conditions studied

• Idiopathic CD4+ Lymphocytopenia — all drugs for Idiopathic CD4+ Lymphocytopenia →
• Cryptococcal Meningitis — all drugs for Cryptococcal Meningitis →
• Warts — all drugs for Warts →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

18 and older, any sex, with Idiopathic CD4+ Lymphocytopenia or Cryptococcal Meningitis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Identification of rare HIV-1-infected patients with extreme CD4+ T cell decline despite ART-mediated viral suppression.
   Lisco A, Wong CS, Lage SL, Levy I, et al · · 2019 · cited 28× · PMID 30996137 · DOI 10.1172/jci.insight.127113
2. Reappraisal of Idiopathic CD4 Lymphocytopenia at 30 Years.
   Lisco A, Ortega-Villa AM, Mystakelis H, Anderson MV, et al · · 2023 · cited 27× · PMID 37133586 · DOI 10.1056/nejmoa2202348
3. Hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells.
   Mudd JC, Busman-Sahay K, DiNapoli SR, Lai S, et al · · 2018 · cited 25× · PMID 30262807 · DOI 10.1038/s41467-018-05528-3
4. Prevalence and pathogenicity of autoantibodies in patients with idiopathic CD4 lymphopenia.
   Perez-Diez A, Wong CS, Liu X, Mystakelis H, et al · · 2020 · cited 18× · PMID 32634122 · DOI 10.1172/jci136254
5. Paradoxical CD4 Lymphopenia in Autoimmune Lymphoproliferative Syndrome (ALPS).
   Lisco A, Wong CS, Price S, Ye P, et al · · 2019 · cited 15× · PMID 31191551 · DOI 10.3389/fimmu.2019.01193
6. Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect.
   Lisco A, Ye P, Wong CS, Pei L, et al · · 2021 · cited 14× · PMID 33471124 · DOI 10.1093/infdis/jiab025
7. T-Cell Depletion in the Colonic Mucosa of Patients With Idiopathic CD4+ Lymphopenia.
   Kovacs SB, Sheikh V, Thompson WL, Morcock DR, et al · · 2015 · cited 13× · PMID 25995198 · DOI 10.1093/infdis/jiv282
8. Helper T cell immunity in humans with inherited CD4 deficiency.
   Guérin A, Moncada-Vélez M, Jackson K, Ogishi M, et al · · 2024 · cited 11× · PMID 38557723 · DOI 10.1084/jem.20231044