余家利Yu, Chia-Li臺灣大學:分子醫學研究所陳朝義Chen, Chao-YiChao-YiChen2010-05-042018-07-092010-05-042018-07-092009U0001-1408200914504200http://ntur.lib.ntu.edu.tw//handle/246246/178725T細胞共同刺激分子群 (Co-stimulatory molecules)及細胞粘著分子(Cell adhesion molecules)在由T細胞及白血球所引起的發炎反應上扮演重要角色。本實驗針對16位活動性類風濕關節炎(rheumatoid arthritis，RA)、20位全身性紅斑狼瘡(Systemic Lupus Erythematosus，SLE)患者及8位正常人，利用酵素連結免疫吸附分析法(ELISA)分析比較其血清中可溶性T細胞共同刺激分子群(sCTLA-4, sCD28, sCD80, sCD86)及細胞粘著分子(sE-selectin, sICAM-1, sVCAM-1)的變化。正常人的血清樣本做對照比較，發現在活動性類風濕關節炎患者，統計上其血清中sCTLA-4的濃度明顯下降(p<0.05)，且sCD80、sE-selectin、sICAM-1及sVCAM-1的濃度明顯上升(p<0.05)。也發現在全身性紅斑狼瘡患者，統計上其血清中sCTLA-4及sE-selectin的濃度明顯下降(p<0.05)，sCD86的濃度明顯上升(p<0.05)。比較活動性類風濕關節炎及全身性紅斑狼瘡患者，顯示出活動性類風濕關節炎患者獨特的分子標記(Bio-Marker)變化，即血清中sCTLA-4的濃度下降，sCD80和三種adhesion molecules (sE-selectin、sICAM-1及sVCAM-1)的濃度上升。同時也顯示出全身性紅斑性狼瘡患者獨特的分子標記(Bio-Marker)變化，即血清中的sCTLA-4和sE-selectin的濃度下降，sCD86的濃度上升。此由本研究發現，可溶性T細胞共同刺激分子群及細胞粘著分子不正常的產生進而活化T細胞及白血球，可能是引起活動性類風濕關節炎及全身性紅斑狼瘡發生的重要途徑，且在活動性類風濕關節炎及全身性紅斑狼瘡上具有特異性。Co-stimulatory molecules connecting with leukocyte adhesion molecules play an important role in responses to T lymphocyte and leukocyte-mediated inflammatory. The aim of the study was to analyze serum concentrations of soluble co-stimulatory molecules (sCTLA-4, sCD28, sCD80, sCD86) and soluble cell adhesion molecules (sE-selectin, sICAM-1, sVCAM-1) among 16 active rheumatoid arthritis (RA) patients, 20 Systemic Lupus Erythematosus (SLE) patients and 8 healthy controls. The analysis method was based on a quantitative sandwich enzyme-linked immunosorbent assay (ELISA).ompared with healthy control subjects (all p<0.05), serum levels of sCTLA-4 was significantly lower in active RA patients, whereas sCD80, sE-selectin, sICAM-1 and sVCAM-1 were significantly higher. In SLE patients, serum levels of sCTLA-4 and sE-selectin were significantly lower whereas sCD86 was significantly higher when comparing with healthy control subjects (all p<0.05).n addition, the comparison of the serum levels of soluble co-stimulatory and cell adhesion molecules between active RA and SLE patients indicates the characteristics of active RA patients, that is the decreasing levels of sCTLA-4 and elevated levels of sCD80, sE-selectin, sICAM-1 and sVCAM-1. The comparison also indicates the characteristics of active SLE patients , that are the decreasing levels of sCTLA-4 and sE-selectin and elevated levels of sCD86.herefore, the study indicates that the aberrant expression of soluble co-stimulatory and cell adhesion molecules activates T cells and leukocytes. And this may be the cause for the inflammation and has the distinctness in active RA and SLE patients.口試委員會審定書……………………………………………… ……………………i 謝……………………………………………………………………………………ii文摘要…………………………………………………………………… ………..iii文摘要…………………………………………………………………… …......…iv一章 緒論…………………………………………………………………………1、前言………………..………………………………………………… ………1、類風濕性關節炎(Rheumatoid Arthritis)介紹……………………………4、全身性紅斑狼瘡(Systemic lupus erythematosus, SLE)介紹…….. ……9、T細胞共同刺激分子群 (Co-stimulatory molecules) ………………… ……13、細胞粘著分子(Cell Adhesion Molecules) …………………………….… …16、研究動機……………………………………………………………….... …18二章 實驗材料方法………………………………………………………......................……19、研究對象……………………………………………………………….……19、檢體收集………..……………………………………………………………19、材料方法…………………………………………………………………..…19、統計分析………………………………………………………………..……20三章 實驗結果…………………………………………………………….……21、正常人、活動性類風濕性關節炎及紅斑性狼瘡患者血清中CTLA-4之濃度………………………………………………………...…21、正常人、活動性類風濕性關節炎及紅斑性狼瘡患者血清中CD28之濃度…………………………………………………………...…22、正常人、活動性類風濕性關節炎及紅斑性狼瘡患者血清中CD80之濃度……………………………………………………………...22、正常人、活動性類風濕性關節炎及紅斑性狼瘡患者血清中CD86之濃度…………………………………………………………...…23、正常人、活動性類風濕性關節炎及紅斑性狼瘡患者血清中E-selectin之濃度…………………………………………………………24、正常人、活動性類風濕性關節炎及紅斑性狼瘡患者血清中ICAM-1之濃度…………………………………………………………..24、正常人、活動性類風濕性關節炎及紅斑性狼瘡患者血清中VCAM-1之濃度……………………………………………………….…25八、活動性類風濕關節炎及全身性紅斑狼瘡患者血清中oluble costimulatory molecules及Soluble adhesion olecules濃度變化之異同…………………………………...….………26四章 討論………………………………………………………………………28考文獻…………………………………………………………………………..…34表………………………………………………………………………………..…42錄……………………………………………………………..……………………53表附錄 目錄一. 類風濕性關節炎的病理機轉………………………………………...……42二. CD28及CTLA-4調控T細胞的活化……………………………...……43三. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡(SLE)患者血清中sCTLA-4的濃度分佈……………………..…44一. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡 (SLE)患者血清中sCTLA-4濃度統計比較表…………………44四. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡(SLE)患者血清中sCD28的濃度分佈…………………………45二. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡 (SLE)患者血清中sCD28濃度統計比較表……………………45五. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡(SLE)患者血清中sCD80的濃度分佈……………………………46三. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡 (SLE)患者血清中sCD80濃度統計比較表……………….……46六. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡(SLE)患者血清中sCD86的濃度分佈……………………………47四. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡(SLE)患者血清中sCD86濃度統計比較表………………………47七. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡(SLE)患者血清中sE-selectin的濃度分佈……………………..…48五. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡(SLE)患者血清中sE-selectin濃度統計比較表……………….…48八. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡(SLE)患者血清中sICAM-1的濃度分佈…………………………49六. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡 (SLE)患者血清中sICAM-1濃度統計比較表……………….…49九. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡(SLE)患者血清中sVCAM-1的濃度分佈………………….……50七. 正常人(Normal)、活動性類風濕性關節炎(aRA)及全身性紅性狼瘡 (SLE)患者血清中sVCAM-1濃度統計比較表…………………50八 活動性類風濕性關節炎(aRA)及全身性紅斑狼瘡(SLE)患者清中Soluble costimulatory molecules及Soluble adhesion olecules濃度變化之異同………………………………………….………51九 本研究之活動性類風濕關節炎(aRA)及全身性紅斑狼瘡(SLE)者血清中 Soluble costimulatory　molecules 及Soluble adhesionolecules濃度變化結果與文獻研究結果之異同比較………………………52十. 針對類風濕關節炎疾病治療之作用標的位…………………………...……53圖十一. 現行針對全身性紅斑狼瘡疾病之免疫療法機制…………………...……54application/pdf1272070 bytesapplication/pdfen-US共同刺激因子粘著因子soluble co-stimulatory factorsadhesion moleculeshttp://ntur.lib.ntu.edu.tw/bitstream/246246/178725/1/ntu-98-P96448013-1.pdf