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研究生:湯惠斐
研究生(外文):Hui-Fei Tang
論文名稱:探討PRA預測國人移植後排斥反應與移植器官存活率的相關性
論文名稱(外文):Correlation of rejection and survival rate on organ post- transplantation in Taiwan by panel reactive antibody detection
指導教授:何元順
指導教授(外文):Yuan-Soon Ho
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:醫學技術學系
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:112
中文關鍵詞:群組反應性抗體存活率人類白血球抗原排斥
外文關鍵詞:PRAHLArejectionsurvival
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人類白血球抗原(Human Leukocyte Antigen)HLA組織相容基因檢測及抗體篩選是移植手術前實驗室重要的工作。器官移植研究中證實,在移植後HLA抗體的發展是反覆而持續的,有許多報告已經建議 HLA 抗體的存在與移植後器官存活有密切關係。而且,在移植前群組反應性抗體 Panel Reactive Antibody(PRA)的存在;與手術後產生排斥的機率及發生移植失敗結果有相關。這項研究將檢測群組反應性抗體,調查於移植手術前及術後持續反應預測異體器官移植失敗之間的相互關係。材料和方法︰持續追蹤從2004年10月到2007年4月,所有的器官移植接受者。於術前及術後每隔一個月連續收集血清冷凍保存。所有血清使用ELISA固相免疫分析法檢測 PRA,使用chi square 或Fisher exact test精確的比較差別變項。當 P值<0.05表示具統計顯著差異。結果︰44位移植病患中有27位男性和17個女性,43.6 (19-66歲)的平均的年齡。所有患者一年存活率81.1%。手術前PRA陽性檢測率(16.2%),失敗率為57.1% (4/7),相對於術前PRA陰性患者術後失敗率13.3% (4/30)。統計p=0.024(p<0.05)。移植手術後PRA陽性共6位,失敗率為83.3% (5/6),手術後PRA陰性患者器官失敗率為9.7% (3/31),統計其p=0.0007(p<0.05) 討論:實驗結果顯示器官(心臟、腎臟)異體移植之失敗與PRA的存在之間有重要的相互關係(p<0.05)。各移植中心於移植手術前篩檢PRA陽性病患,移植後定期監測PRA反應及生化指標性檢查之變化,可以早期預測移植後排斥反應,是監控穩定的器官移植演化的一種有用的方法。因受限於時間有限及個案數量太少涉及長期的器官異體移植失敗很多免疫學和非免疫學元素,及各種免疫抑制之使用,都可能導致排除PRA反應預測移植失敗的協定,需要更多移植個案和更長時間的後續行動證明。
The development of antibodies to human leukocyte antigens (HLA) after transplantation verified ongoing reactivity against the transplant, the presence of HLA antibodies correlates with poor graft survival. The presence of HLA antibodies prior to transplantation has been linked to worse post-transplant outcomes in many solid organ transplants. This study was to investigate the relationship between organ allograft failure and pre-transplantation panel reactive antibody (PRA) reactivity. METHODS: From October 2004 to Aril 2007, a total of 44subjects were enrolled. There were 27 males and 17 females, with a mean age of 43.6 years (range 19 -66). Organ allograft recipients were enrolled. PRA was determined in batch using a commercially available kit. Categorical variables were compared using chi square or Fisher exact test as appropriate. A p value less than 0.05 was considered statistically significant. RESULTS: Of all, one-year graft survival rate was 81.1%, and 7 (16.2%) had positive PRA tests before transplantation. One-year graft failure rate was 57.1% (4/7) for those with pre-transplantation PRA positivity and 13.3% (4/30) for those having pre-transplantation PRA negativity, p value was 0.024 (p<0.05). Graft failure rate was 83.3% (1/6) for those with post-transplantation PRA positivity and 9.7% (3/31) for those having post-transplantation PRA negativity, p value was 0.0007 (p<0.05). There was a significant correlation between renal allograft failure and the presence of PRA. CONCLUSIONS: PRA reactivity was significantly associated with one-year graft failure (p<0.05). Our results suggest that a routine post-transplant AHG-PRA test offers an early risk assessment of rejection episodes and may be a useful method for monitoring the solid organ transplant evolution. The limited case numbers and time of follow-up precludes confirming the association of pre-transplantation PRA and allograft failure. Furthermore, many immunologic and nonimmunologic factors, other than PRA, are involved in long-term kidney allograft failure. To enroll more case and longer follow-up are needed.
致 謝 I
中文摘要 II
Abstract IV
目錄 VI
圖表目錄 IX
縮寫表 X
第一章 緒論 1
壹、概說 1
貳、抗HLA抗體篩選在器官移植中的意義: 4
第二章 文獻探討 7
壹、器官移植Organ transplant 7
貳、移植的種類: 7
叁、主要受移植的器官及組織(Major organs and tissues transplanted) 8
肆、捐贈者種類: 8
伍、移植之重要里程碑: 9
陸、HLA的臨床意義(人類白血球抗原Human Leukocyte Antigen) 10
柒、排斥反應 17
捌:排斥反應的種類: 22
玖:免疫抑制藥物: 26
拾:移植免疫學的檢查 27
拾壹;研究目的 37
第三章 研究方法 39
壹、病患收集 39
貳、檢體採集保存 40
叁、檢測方法 41
肆、統計分析 52
第四章 分析與結果 53
壹、樣本資料分析: 53
貳、HLA 抗原分型檢查 54
叁、交叉試驗Cytotoxic donor crossmatches 54
肆、HLA 抗體篩檢 55
伍、病理切片結果 56
陸、血清creatinine濃度分析 58
第五章 討論 59
壹、PRA檢測與移植器官存活相關性 59
貳、PRA與細胞性排斥 60
叁、HLA抗原分佈頻率與抗體產生 62
肆、HLA配對檢驗 62
第六章 結論與建議 69
參考文獻 87
附錄 102
壹、心臟移植分配原則: 102
貳、腎臟移植分配原則: 105
叁、HLA組織抗原符合配對定義表(HLA Mismatch Definitions) 109
肆、研究受試者說明同意書 110
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