2012-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/700055摘要：過敏性紫斑症（Henoch-Schönlein purpura）是一種好發於兒童的全身性小血管炎。目前並無一項專一檢查數據可用於確切診斷過敏性紫斑症，而且真正致病原因目前仍不清楚。典型的病理切片顯示小血管周圍浸潤著大量的中性白血球，螢光免疫染色可於血管壁發現IgA 球蛋白及補體C3 的沉積，另外，約一半以上的病童急性期血清中的IgA 會明顯上升。綜合以上，過敏性紫斑症是一種免疫相關疾病，特別是與「IgA」有關的免疫疾病。先前的研究已發現IgA 抗牛心酯抗體及IgA 抗血管內皮細胞抗體會出現於疾病急性期，但這兩類抗體分別為一群組成複雜且功能不同的自體抗體。最近，我們發現過敏性紫斑症急性期血中的IgA 會與2 醣蛋白I（2GPI）結合，且病童的IgA 抗2GPI抗體濃度分別與IgA 抗牛心酯抗體濃度及IgA 抗血管內皮細胞抗體濃度呈高度正相關。因此我們假設2GPI 是過敏性紫斑症重要的自體抗原。為了要驗證此假說，首先我們將偵測並比較IgA 抗2GPI 抗體在過敏性紫斑病童及不同對照組的表現，釐清病童IgA 與2GPI、牛心酯、及血管內皮細胞之間的結合及相互的影響；接著，我們將進一步找尋與IgA 結合的抗原決定部位；分析2GPI 對病童T 細胞的作用。另一方面，我們亦將確定IgA 抗2GPI 抗體在過敏性紫斑症致病機轉中的角色，以及此自體抗體在臨床的應用價值。完成此計畫，將對過敏性紫斑有更深一層的認識，並且有機會研發出疾病專一的診斷試驗工具。<br> Abstract: Henoch-Schönlein purpura (HSP) is a systemic form of small vessel vasculitis thatprimarily affects children. Nowadays, there is no specific test for the diagnosis of HSP, andthe etiology and pathogenesis of this disease are still unknown. According to the pathologicaland laboratory findings of IgA and complement (C3) deposits on small vessel wall,polymorphonuclear neutrophils infiltration around the vessel, and increased serum levels ofIgA during the acute stage, it is speculated that HSP is an immune-mediated vasculitis,especially is IgA-related. Previous studies have shown that some circulating IgA from acutebut not convalescent sera of HSP would bind to cardiolipin and endothelial cells. However,anti-cardiolipin antibodies and anti-endothelial cell antibodies are respectively aheterogeneous group of antibodies that bind to various antigens with different functions.Recently, we found that IgA from acute HSP can bind well to 2 glycoprotein I (2GPI).2GPI is a plasma protein produced by liver and will bind to negatively chargedphospholipids like cardiolipin. Interestingly, we also found the serum levels of IgAanti-2GPI antibodies are well correlated to both IgA anti-cardiolipin antibodies and IgAanti-endothelial cell antibodies. Based on these findings, we hypothesize that 2GPI might bean important autoantigen in HSP. To test the hypothesis, we will first analyze the presence ofIgA anti-2GPI antibodies in HSP, other disease controls, and healthy controls. Then, we willclarify the binding characteristics of HSP-derived IgA to 2GPI, cardiolipin, and endothelialcells. Moreover, we will identify the binding epitopes of 2GPI for IgA. The effects of 2GPIon patients’T cells will also be analyzed. On the other hand, we will evaluate the clinicalsignificance and pathogenic role of IgA anti-2GPI antibodies in HSP. The results of thisproject will provide some clues for a better understanding of HSP and may be helpful todesign a specific diagnostic test for HSP.過敏性紫斑症beta2醣蛋白I自體抗原IgA抗體