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

Official 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

Study Design

• Study Type: OBSERVATIONAL
• Enrollment: 950 participants

Primary Outcomes

• CD4 <300/microliters or < 20% of total T cells and their blood (Baseline and annually)

Secondary Outcomes

• Determine CD4+ T cell turnover, survival, functionality and cytokineresponsiveness in selected ICL patients. (Baseline and annually)
• Investigate ICL immune cell homeostasis and trafficking by immunologic studies including tissue biopsies and the utilization of ahumanized mouse model. (Baseline and annually)
• Establish the prognosis 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. (Baseline and annually)
• Determine whether measurable immunologic parameters correlate with the development of opportunistic infections or other co-morbidities (Baseline and annually)
• Determine the relationship between ICL and the microbiome. (Baseline and annually)

Eligibility Criteria

* 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.

Trial Locations

• National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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