2014-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649167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。目前並無專一實驗室檢查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。先前我們的研究發現過敏性紫斑症急性期血中的 IgA會與2醣蛋白 I（2 glycoprotein I, 2GPI），特別是其中某些片段的胜肽緊密結合，且透過2GPI這些 IgA可黏附到血管內皮細胞上，接著，一方面透過MEK/ERK 訊息傳遞路徑促進血管內皮細胞分泌大量IL-8，另一方面在補體存在的情況下造成內皮細胞傷亡。另外，我們亦發現 TH3及 TH17細胞在紫斑症急性期也扮演重要的角色。從以上的研究成果我們逐步釐清「專一性免疫」（adaptive immunity）在此血管炎致病過程中的角色扮演。不過，典型的病理切片上發現除了 IgA外，補體 C3亦會沉積於血管壁上。另外，嗜中性白血球大量浸潤於血管周邊及血管壁中更是此血管炎的特徵。而上述專一性免疫系統的活化是需要樹突細胞的幫忙。因此，我們認為過敏性紫斑症的形成，「非專一性免疫」（innate immunity）的參與是不可或缺。初步發現紫斑症病童急性期血漿中的 C3a及 C5a明顯高於緩解期及對照組。為了進一步確定非專一性免疫系統在疾病中的角色，我們提出一為期三年的計畫分別探究補體系統、嗜中性白血球、以及樹突細胞在過敏性紫斑症中的活化情況。接著，透過實驗的設計釐清三者在致病機轉中的貢獻，包括其與血管內皮細胞、彼此之間、以及與專一性免疫系統間的相互作用。另一方面，我們也將分析非專一性免疫系統的活化與臨床症狀及嚴重度的相關性。完成此計畫，將更清楚過敏性紫斑的致病機轉；未來對疾病的診斷、治療、及追蹤將有實質的助益。 <br> Abstract: Key words: Henoch-Schönlein purpura, complement, neutrophil, dendritic cell Henoch-Schönlein purpura (HSP) is a systemic form of small vessel vasculitis that primarily affects children. Nowadays, there is no specific test for the diagnosis of HSP, and the etiology and pathogenesis of this disease are still unknown. Previously, we have found that HSP-derived IgA bound well to 2 glycoprotein I (2GPI) and several fragmental peptides of 2GPI. These 2GPI-reactive IgA then crossly reacted with endothelial cells (EC) to induce IL-8 production by EC through the MEK/ERK signaling pathway and complement-dependent EC lysis. In addition, type 3 T helper (TH3) cells and TH17 cells were also found to be involved in the pathogenesis of HSP. Accordingly, the role of adaptive immunity in HSP is now clarified step by step. However, in addition to IgA, the deposits of complement 3 (C3) are often shown on skin and renal biopsies. Other pathohistological characteristics of HSP include the infiltration of neutropils around the vessels and in the vessel walls. Besides, dendritic cells are critical in the activation of cellular and humoral immunity. Combined, innate immunity is likely to be involved in the development of HSP. We found recently that plasma levels of C3a and C5a were significantly higher in HSP children at acute stage than those at convalescent stage and in healthy controls. To further determine the role of innate immunity in HSP, we propose a 3-year project; first, we will evaluate the activation status of complement system, neutrophils, and dendritic cells in HSP. Next, experiments will be designed to evaluate the pathogenic mechanisms that above 3 innate immune systems (complement system, neutrophils, and dendritic cells) contribute, especially focusing on their interaction with EC, the interaction between each other, and their interaction with adaptive immune system. Finally, we will analyze the association between some activation parameters of innate immunity (like C3a, C5a, NADPH oxidase activity, levels of myeloperoxidase, and levels of reactive oxygen species) and clinical symptoms and disease severity. The results of this project will provide some clues for a better understanding of HSP and may be helpful to the diagnosis, treatment, and disease follow-up of HSP.過敏性紫斑症補體系統嗜中性白血球樹突細胞Henoch-Schönlein purpuracomplementneutrophildendritic cell