View clinical trials related to Idiopathic CD4+ Lymphocytopenia.
Filter by:Definition: Idiopathic CD4+ T lymphocytopenia (ICL) is an immune deficiency first described in 1992 and characterized by the US Centers for Disease Control (CDC) as absolute CD4+ T-lymphocyte count < 300/mm3 or < 20% of total T cells on more than one cell count; no evidence of infection with HIV-1/2 or human T-cell lymphotropic 1/2 (HTLV-1/2); and lack of a defined immune-deficiency disease or therapy for lymphocytopenia. Epidemiologic, clinical and immunological characteristics of the syndrome were described in 1993 and ICL is now considered a heterogeneous syndrome not caused by an infectious agent. Patients with ICL may show opportunistic infections such as disseminated Cryptococcus neoformans infection, Pneumocystis jiroveci pneumonia and John Cunningham (JC) virus infection as a result of profound cell-mediated immune-response deficiency. Few studies have focused on the pathophysiology of ICL. CD4+ T-lymphocyte phenotyping revealed increased CD95 expression that could be responsible for excess apoptosis leading to lymphocytopenia. Moreover, the membrane expression of C-X-C chemokine receptor type 4 (CXCR4) was found impaired in T lymphocytes with ICL, and CXCR4 trafficking was improved with interleukin 2 (IL-2) treatment in some patients. Recently, mutations in nunc119, MAGT1 and Rag were found associated with CD4+ T lymphocytopenia. In a prospective study of 39 patients, CD8+ T lymphocytopenia (<180/mm3) and degree of CD4+ T-cell activation measured by human leukocyte antigen DR (HLA-DR) expression was found associated with poor prognosis. ICL is a heterogeneous disorder often associated with deficiencies in CD8+, CD19+, and/or NK cells. Long-term prognosis may be related to initial CD4+ and NK cell deficiency. Larger studies are needed to better identify the patients who might benefit from IL-2 therapy. This is why the investigators conduct the Lympho-4 study, in which the investigators plan to include 200 patients with a suspected/proven diagnosis of ICL.
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.