2016-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649315摘要：人類白血球組織抗原(human leukocyte antigen; HLA)抗體(human leukocyte antigen)是腎臟移植後急性與慢性排斥的主因。如果移植病人產生針對之捐者特異性抗體(donor-specific antibody; DSA)，則其移植腎臟的存活期明顯縮短。因此，監測甚至避免捐者特異性抗體的產生是移植照顧極為重要的課題。人類白血球組織的抗原可以依其抗原分型分類，例如HLA-A11, -A24等; 而依抗體間的交叉反應，各分型間可以分成數個群組--稱為交叉反應群組(cross-reactivity group; 縮寫為CREG)。近來對HLA抗體研究及病人產生抗體其交叉反應的分析，已了解HLA抗體的作用是對應至抗原點(epitope)，即由相鄰近的胺基酸共組成的結構。不同的HLA抗原分型間可能有自已特有的抗原點，也有與其他分型共有的抗原點。利用結構性抗原點的觀念分析腎臟移植捐者與受者的HLA相容性，或是捐者特異性抗體可以得到更完整與可靠的預測結果。本研究的重點即是應用電腦程式析腎臟移植病人HLA 抗原相容性與抗體特異性，以提供更佳的移植配對策略及抗體監測治療的依據。研究內容包括1)以結構抗原點分析腎臟移植捐者與受者間結構性抗原點之相容性，以其對移植器官的存活率之影響2)腎臟移植捐者與受者間結構性抗原點之相異程度及抗原點差異量(epitope load)與病人HLA 抗體產生抗體特異性之相關性3)利用電腦模型分析高致敏者(hersensitized patient)其體內抗體對異之結構抗原點，並制定配合策略(algorithm)設計電腦預測模式，根據病人與捐者組織抗原型配對情形，建立特定抗原點抗體形成的預測模式<br> Abstract: Human leukocyte antigens (HLA) antibodies are produced following exposure to foreign HLA antigensafter transplantaion, pregnancy and blood transfusion. They are strongly associated with transplant rejectionand decreased graft survival. It is essential to monitor post-transplant HLA antibodies, especially the donorspecific antibody.HLA antibodies can be characterized as antigen-specific (eg. anti-A11, anti-B7 and anti-DR1) or ascross-reacting antigen group-specific (eg. anti-A2 CREG and anti-B7 CREG). HLA antigens can bestructurally characterized as based on molecular modeling and amino acid sequence differences betweenantibody-reactive and nonreactive alleles. These structurally-defined epitopes are key elements of HLAepitopes that elicit specific antibodies. They are annotated by position numbers in the amino acid sequenceand standard single-letter polymorphic residues within the proximity of 3D structures.Application of structural epitope-based concept in the analysis of serum antibody reactivity of sensitizedpatients and the identification of potential donors with acceptable epitope mismatches has been proven usefuland even outperform the traditional antigen-based analysis.This project aims to utilize computer program to analyze the HLA antibody specificities andhisto-compatibilities of kidney transplant patients. This can provide better matching strategy andpost-transplant donor specific antibody surveillance. This project includes: 1) analysis of serum antibodyreactivity of sensitized patients and the identification of potential donors with acceptable epitope mismatches2) quantitative determination of the degree of a mismatch (i.e. epitome load) and its influence on graftsurvival 3) establishment of a computer model to predict antibody response to HLA mismatch.人類白血球組織抗原抗體捐者特異性抗體抗原點腎臟移植Human leukocyte antigenDonor specific antibodyepitopeKidney transplantation