https://scholars.lib.ntu.edu.tw/handle/123456789/194462
標題: | 兒童過敏性紫斑症血管內皮細胞自體抗原之探討(1/2) | 作者: | 楊曜旭 | 關鍵字: | 過敏性紫斑症;內皮細胞;自體抗體;自體抗原 | 公開日期: | 2004 | 出版社: | 臺北市:國立臺灣大學醫學院小兒科 | 摘要: | 過敏性紫斑症是一種好發於兒童的全身性小血管炎。臨床表現上,常於下肢及 臀部出現典型的紫斑,病童也常伴隨關節發炎、關節痛、四肢水腫、腹部疼痛、 血便等症狀。更甚者,會侵犯腎臟造成腎絲球腎炎或是侵犯腸胃道造成腸胃穿恐 等嚴重之併發症。病理切片上可發現多型性白血球浸潤在小血管週邊,血液中 IgA 抗體會明顯升高,同時亦發現含IgA 的免疫複合體會沉積於血管基底膜。治 療上,以支持性療法為主,類固醇或是免疫抑制劑通常只使用於嚴重的病例。 過敏性紫斑症的致病機轉到目前為止仍不清楚,只知道是因為一些免疫系統不 正常的活化所造成。臨床上的研究觀察發現:在病發之前,大部份的病童都有上 呼吸道感染的症狀。而且大多於秋冬季節發作。因此推論過敏性紫斑症可能跟某 種病原體的感染有關:在病原體進入體內之後,啟動了免疫系統,造成細胞激素 的分泌,進而誘發抗體的產生,尤其是IgA 抗體,而抗體與血管內皮細胞的交互 作用導致血管的發炎與破壞。 本研究的主要目的是希望藉由各種實驗設計以確定過敏性紫斑症的致病機 轉。首先建立人類血管內皮細胞的培養,並收集患病兒童急性期及緩解期之血 清。接著以螢光染色法及以內皮細胞為基底之酵素免疫法,確定病童抗內皮細胞 抗體的存在,並探討抗體與血管內皮細胞交互作用的機轉。之後將進一步建立病 童抗體資料庫。用所建立的病童抗體資料庫或含自體抗體之病人血清篩選內皮細 胞為抗原蛋白, 純化自體抗體, 配合西方印漬法(SDS-PAGE and 2-D immunoblotting)進一步找出內皮細胞之抗原決定部位。完成此研究,將可進一 步釐清過敏性紫斑症的致病機轉。對於疾病的預防與治療將有實質的助益。 先前九個月的時間,我們分別完成(1)分離並維持人類內皮細胞的培養,(2) 收集二十位病童不同時期的血清,(3)確定病童急性期血清中含有IgA 抗血管內 皮細胞抗體,(4)釐清抗體(病童急性期血清)與內皮細胞作用關係(Yang YH, et al. Ann Rheum Dis 2004),(5)分離內皮細胞各層之蛋白質。未來將按照進度 建立病童抗體資料庫。用所建立的病童抗體資料庫或含自體抗體之病人血清篩選 內皮細胞為抗原蛋白,配合西方印漬法進一步找出內皮細胞之抗原決定部位。 Henoch-Schönlein purpura (HSP) is one of the most common types of vasculitis in childhood. Histologically, it reveals the change of leukocytoclastic vasculitis, and has been well regarded as a specific clinicopathological entity by the vascular deposition of immunoglobulin (Ig) A-dominant immune complexes and elevated serum IgA level. The pathogenesis of HSP remains undetermined. Clinical observations have found striking seasonal variations in HSP, with most cases occurring in the winter and autumn. HSP has also been associated with a history of preceding infections, especially upper respiratory tract infection. These results raise the possibility of infection as a direct cause or a potential trigger of this disease. It is speculated that some microorganisms with specific antigenic structures, which mimic some components of blood vessel enters the respiratory or gastrointestinal tract and stimulates the T cells residing in the mucosa. Inflammatory responses are elicited with the participation of various immunocompetent cells and their humoral counterparts. The antibodies, and other immune cells against the microorganisms may cross-react with the specific component of the vessel and lead to the inflammation of vessels. The aims of this project are to design experiments to determine the pathogenesis of childhood HSP. In the previous 9 months, we have completed the following works: (1) we have set up and maintain the culture of human endothelial cells. (2) The serum samples of 20 HSP children were collected at different stages. (3) By means of immunofluorescence assay and cell-based ELISA, we have confirmed that IgA anti-endothelial cell antibodies developed during the acute stage of HSP. (4) The interactions of antibodies (acute sera of patients) and endothelial cells have been investigated (Yang YH, et al. Ann Rheum Dis 2004). (5) The membrane protein/cytoplasmic protein have been separated and collected. In the future, we will further establish the antibodies library of children with HSP. Then, the autoantibodies against EC will be determined by the screen of the HUVEC cDNA library or EC membrane and cytoplasmic proteins. Using the screened antibodies or sera of patients at the acute stage, the disease-specific antigen will be determined by Western blotting (SDS-PAGE and 2-D immunoblotting). If this study can be performed and completed smoothly, the pathogenesis of this common childhood vasculitis will be much clear, and that are very important in the prevention and the treatment of this disease. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/22899 | 其他識別: | 922314B002223 | Rights: | 國立臺灣大學醫學院小兒科 |
顯示於: | 醫學系 |
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