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供体特异性抗体在肠道移植中的作用:加利福尼亚大学洛杉矶分校的经验及文献综述

The Role of Donor-Specific Antibodies in Intestinal Transplantation: Experience at the University of California Los Angeles and Literature Review.

作者信息

Cheng Elaine Y, Kaneku Hugo, Farmer Douglas G

出版信息

Clin Transpl. 2014:153-9.

Abstract

Intestinal transplantation is a viable treatment strategy for patients with irreversible intestinal failure for whom parenteral nutrition is no longer an option. Although improvements have been made in short-term post-transplant survival outcomes, long-term allograft loss, mainly to acute or chronic rejection, remains a major obstacle to successful transplantation. In all types of solid organ transplants, there is increasing evidence that antibodies directed against human leukocyte antigens, and in particular donor-specific antibodies (DSA), contribute to acute and chronic rejection as well as allograft loss. In this single-center review of intestinal transplant recipients, we report that the presence of pretransplant circulating DSA and the de novo induction of DSA posttransplant are both associated with increased risks of allograft loss. Although the cumulative incidence of acute rejection was not significantly affected by the presence of DSA, the power of this single-center study may be limited. Prospective, multicenter studies are needed to further elucidate the role of DSA in intestinal transplant recipients. In the published literature, there is a clear link between the presence of pre-formed DSA and early injury to the mucosal vasculature of the allograft. Two groups have reported an association between pretransplant DSA and the frequency of acute rejection episodes and subsequent graft loss. Similarly, studies investigating the effects of de novo DSA have demonstrated a relationship between the presence of post-transplant circulating antibodies and the occurrence of acute rejection and the risk of allograft failure. The use of a liver-containing graft appears to facilitate the clearance of pre-formed antibodies and prevents the de novo induction of post-transplant antibodies. The most recent report stated that the de novo induction of DSA is concurrently accompanied by signs or rejection, such that the detection of circulating antibodies may signify impending graft injury, and supports the potential utility of DSA as a non-invasive biomarker for rejection in intestinal transplantation.

摘要

肠道移植是不可逆肠衰竭患者的一种可行治疗策略,对于这些患者而言,肠外营养已不再是一种选择。尽管移植后短期生存结局有所改善,但长期移植物丢失,主要是由于急性或慢性排斥反应,仍然是移植成功的主要障碍。在所有类型的实体器官移植中,越来越多的证据表明,针对人类白细胞抗原的抗体,尤其是供体特异性抗体(DSA),会导致急性和慢性排斥反应以及移植物丢失。在这项对肠道移植受者的单中心回顾中,我们报告移植前循环DSA的存在以及移植后DSA的从头诱导均与移植物丢失风险增加相关。尽管急性排斥反应的累积发生率不受DSA存在的显著影响,但这项单中心研究的效力可能有限。需要进行前瞻性、多中心研究以进一步阐明DSA在肠道移植受者中的作用。在已发表的文献中,预先形成的DSA的存在与同种异体移植物黏膜血管的早期损伤之间存在明确联系。两组报告了移植前DSA与急性排斥反应发作频率及随后的移植物丢失之间的关联。同样,研究新发DSA作用的研究表明,移植后循环抗体的存在与急性排斥反应的发生以及同种异体移植物失败的风险之间存在关联。使用含肝移植物似乎有助于清除预先形成的抗体,并防止移植后抗体的从头诱导。最近的报告指出,DSA的从头诱导同时伴有排斥迹象,因此循环抗体的检测可能预示着即将发生的移植物损伤,并支持DSA作为肠道移植排斥反应的非侵入性生物标志物的潜在效用。

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