Analysis of Clinical and Immunological Characteristics, as Well as Pathophysiological Mechanisms in a French Cohort of Patients With Idiopathic CD4 Lymphocytopenia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Clinical, immunological and follow up characteristics of all patients
研究概览
简要总结
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.
详细描述
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.
ICL is a heterogeneous disorder often associated with deficiencies in CD8+, CD19+, and/or NK cells. Thus, ICL does not correspond to a unique disease but more probably to a number of different conditions with distinct underlying mechanisms. This is why the investigators decided to launch the Lympho-4 study, in which the investigators plan to include 200 patients with a suspected/proven diagnosis of ICL.
The aim of the study will be to
- identify patients in whom the diagnosis of ICL is confirmed using an algorithm developed by a group of multidisciplinary experts.
- describe and compare clinical, immunological and follow up characteristics of patients in whom the diagnosis of ICL was confirmed vs patients in whom the diagnosis of ICL is not confirmed.
The investigators will also investigate :
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Idiopathic CD4 lymphocytopenia defined 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.
- •Male and female patients can be included
- •Children and adults can be included
- •Hospitalized or outpatient
排除标准
- •CD4+ lymphocytopenia due to another condition (HIV infection, sarcoidosis, malignant lymphoma).
- •Ongoing treatment possibly responsible for CD4 lymphocytopenia.
- •CD4+ lymphocytopenia related to primary immune deficiency
- •Absence of consent, of inability to obtain informed consent from the patients or the right holders.
- •Absence of affiliation to a social security regimen of the patient or the right holder.
研究组 & 干预措施
Idiopathic CD4 lymphocytopenia
Constitution of a biobank of frozen cells, plasma and serum samples
干预措施: Constitution of a biobank of frozen cells, plasma and serum samples (Biological)
Genetic Study
High rate genome wide genetic screening, investigation of mutations associated with identified primary immune deficiencies (adenosine deaminase et class II MHC)
干预措施: Genetic study (Genetic)
结局指标
主要结局
Clinical, immunological and follow up characteristics of all patients
时间窗: 1 year
Describe and compare clinical, immunological and follow up characteristics of patients in whom the diagnosis of ICL was confirmed as compared to those in whom the diagnosis of ICL was not confirmed.
Idiopathic CD4+ T lymphocytopenia Diagnosis
时间窗: 1 year
Identify patients in whom the diagnosis of ICL is confirmed using an algorithm developed and applied by a multidisciplinary group of experts
次要结局
- Response to IL-2 or IL-7 treatment(1 year)
- Incident cases of ICL in first degree relatives(1 year)
- Thymic volume and correlation with CD4+ level(1 year)
- Analysis of differentiation and activation of T and B lymphocytes(1 year)