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

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.