Meabed Mohamed H, Taha Gamal M, Mohamed Seham O, El-Hadidy Khaled S
Department of Pediatrics, Faculty of Medicine, Bani Suef University, Bani Suef, Egypt.
Hematology. 2007 Aug;12(4):301-7. doi: 10.1080/10245330701383957.
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.
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 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.
The expression of CD4 + CD154+ and CD4 + CD154+/CD4+ on PB T 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).
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.
CD40 - CD40L系统在包括免疫反应在内的多种细胞和生物学过程中具有多效性作用。在免疫系统中，这些分子是其体液免疫和细胞免疫分支之间的关键联系。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，其特征是由于抗血小板自身抗体导致抗体诱导的血小板破坏和清除，这些自身抗体与循环中的血小板结合，导致它们被网状内皮系统破坏。尽管其具有临床重要性，但ITP的诊断是一种排除性诊断，因此不可避免地存在潜在困难。CD40是一种细胞表面受体，属于肿瘤坏死因子受体（TNF - R）家族，最初在B淋巴细胞上被鉴定并进行功能表征。CD40配体（CD40L/CD154）是TNF超家族的成员，是一种在活化的CD4 + T淋巴细胞上表达的细胞膜分子，对于B淋巴细胞的T细胞依赖性活化至关重要。因此，现在认为CD40 - CD40L相互作用在ITP免疫调节中发挥更重要的作用。
使用流式细胞术（FCM）分别检测外周血（PB）T淋巴细胞和B淋巴细胞上CD154和CD40的表达。对30例急性ITP儿科患者、30例慢性ITP成年患者以及20例年龄和性别匹配的健康对照进行了针对CD4 + T淋巴细胞上血小板相关CD154（CD40L）和CD19 + B淋巴细胞上CD40的抗原特异性检测。
与对照组相比，急性和慢性ITP患者外周血T淋巴细胞上CD4 + CD154 +和CD4 + CD154 + /CD4 +的表达，以及外周血B淋巴细胞上CD19 + CD40 +和CD19 + CD40 + /CD19 +的表达显著更高，且急性患者高于慢性患者（p < 0.001）。
CD40 - CD40L相互作用在某些自身免疫性疾病的病理过程中起重要作用。ITP是一种自身免疫性疾病，其特征是抗血小板自身抗体导致血小板破坏增加，这些自身抗体主要靶向血小板表面抗原。据推测，血小板相关CD154能够诱导B淋巴细胞的CD40依赖性增殖。因此，ITP患者中血小板相关CD154的表达增加，并且能够驱动该疾病中自身反应性B淋巴细胞的活化。这些发现对于阐明ITP患者的致病过程以及开发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免疫调节策略，许多研究结果表明，CD40/CD154阻断疗法通过选择性抑制针对血小板抗原的自身反应性T和B淋巴细胞，对ITP可能有效。
