Autoimmune thrombocytopenia: Flow cytometric determination of platelet-associated CD154/CD40L and CD40 on peripheral blood T and B lymphocytes
Autoimmune thrombocytopenia: Flow cytometric determination of platelet-associated CD154/CD40L and CD40 on peripheral blood T and B lymphocytes
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DOI：
10.1080/10245330701383957
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发表时间：
2007-01-01
期刊：
影响因子：
1.9
通讯作者：
El-Hadidy, Khaled S.
中科院分区：
文献类型：
--
作者：
Meabed, Mohamed H.;Taha, Gamal M.;El-Hadidy, Khaled S.
背景和目的：CD40 - CD40L系统在多种细胞和包括免疫应答在内的生物过程中具有多效性作用。在免疫系统内，这些分子代表了体液和细胞臂之间的关键联系。免疫性或特发性血小板减少性紫癜（ITP）是一种自身免疫性疾病，其特征是抗体诱导的血小板破坏和清除，这是由于抗血小板自身抗体与循环血小板结合，导致其被网状内皮系统破坏。尽管ITP具有重要的临床意义，但ITP的诊断是一种排除，因此不可避免地与潜在的困难相关。CD40是一种细胞表面受体，属于肿瘤坏死因子受体（TNF- R）家族，最早在B淋巴细胞上发现并功能表征。CD40-配体（CD40L/ CD154）是TNF超家族成员之一，是在活化的CD4 + T淋巴细胞上表达的细胞膜分子，对T细胞依赖性的B淋巴细胞活化至关重要。因此，现在认为CD40 - CD40L相互作用在ITP免疫调节中起着更重要的作用。设计与方法：采用流式细胞术（FCM）检测外周血T淋巴细胞和B淋巴细胞中CD154和CD40的表达。在30例急性ITP儿童患者、30例慢性ITP成人患者和20例年龄和性别匹配的健康对照中，对CD4 + T淋巴细胞上血小板相关抗体CD154 （CD40L）和CD19 + B淋巴细胞上CD40进行了抗原特异性检测。结果：急性和慢性ITP患者PBT淋巴细胞CD4 + CD154 +、CD4 + CD154 + / CD4 +、PB - B淋巴细胞CD19+ CD40 +、CD19+ CD40 + / CD19+表达均显著高于对照组，急性和慢性ITP患者表达均显著高于对照组（p < 0.001）。结论：CD40 - CD40L相互作用在某些自身免疫性疾病的病理中起重要作用。ITP是一种自身免疫性疾病，其特征是抗血小板自身抗体引起血小板破坏增加，主要针对血小板表面抗原。推测血小板相关的CD154能够诱导B淋巴细胞的CD40依赖性增殖。因此，血小板相关的CD154表达在ITP患者中增加，并能够在这种疾病中驱动自身反应性B淋巴细胞的激活。这些发现对于阐明ITP患者的致病过程和开发一种阻断致病性抗血小板抗体产生的治疗方法特别有用。阻断CD40/ CD154信号是T细胞介导疾病的一种潜在的免疫调节策略，许多研究结果表明，CD40/ CD154阻断治疗可能通过选择性抑制自身反应性T淋巴细胞和B淋巴细胞对血小板抗原的反应而对ITP有效。
Background and objectives: The CD40 - CD40L system has pleiotropic effects in a variety of cells and biological processes including the immune response. Within the immune system, these molecules represent a critical link between its humoral and cellular arms. Immune or idiopathic thrombocytopenic purpura ( ITP) is an autoimmune disorder characterized by antibody-induced platelet destruction and clearance due to anti- platelet autoantibodies, which bind to circulating platelets resulting in their destruction by the reticuloendothelial system. Despite its clinical importance, the diagnosis of ITP is one of exclusion, thus, inevitably associated with potential difficulties. CD40 is a cell surface receptor that belongs to the tumor necrosis factor-receptor ( TNF- R) family, and that was first identified and functionally characterized on B lymphocytes. CD40- ligand ( CD40L/ CD154), a member of the TNF superfamily, is a cell membrane molecule expressed on activated CD4 + T lymphocytes and is essential for the T cell- dependent activation of B lymphocytes. Therefore it is now thought that CD40 CD40L interactions play a more important role in ITP immune regulation. Design and methods: The expressions of CD154 and CD40 on peripheral blood ( PB) T and B lymphocytes, respectively, were measured using flow cytometry ( FCM). An antigen- specific assay for platelet- associated antibody CD154 ( CD40L) on CD4 + T lymphocytes and for CD40 on CD19 + B lymphocytes was tested in 30 pediatric patients with acute ITP, 30 adult patients with chronic ITP, and in 20 age- and sex- matched healthy controls. Results: The expression ofCD4 + CD154 + andCD4 + CD154 + / CD4 + on PBT lymphocytes, and CD19 + CD40 + and CD19 + CD40 + / CD19+ on PB B lymphocytes were significantly higher in acute and chronic ITP patients compared to controls, and in acute patients compared to chronics ( p < 0.001). Conclusions: CD40 - CD40L interaction plays an important role in the pathology of certain autoimmune diseases. ITP is an autoimmune disease characterized by increased platelet destruction caused by anti- platelet autoantibodies, which mainly target a platelet surface antigen. It is speculated that platelet- associated CD154 is competent to induce the CD40- dependent proliferation of B lymphocytes. Therefore, platelet- associated CD154 expression is increased in ITP patients and is able to drive the activation of autoreactive B lymphocytes in this disease. These findings are particularly useful for clarifying the pathogenic process in ITP patients and for developing a therapeutic approach that blocks pathogenic anti- platelet antibody production. Blockade of the CD40/ CD154 signal is a potential immunomodulatory strategy for T cell- mediated diseases, and many findings suggest that CD40/ CD154 blockade therapy is potentially effective for ITP through selective suppression of autoreactive T and B lymphocytes to platelet antigens.