The role of anti-non-Gal antibodies in the development of acute humoral xenograft rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal antibody neutralization therapy

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	The role of anti-non-Gal antibodies in the development of acute humoral xenograft rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal antibody neutralization therapy
	Chen G 1,2; Sun HT 3; Yang HJ 1; Kubelik D 1; Garcia B 3; Luo YG 1,4; Xiang Y 1; Qian A 1; Copeman L 5; Liu WH 3; Cardella CJ 6; Wang WY 7; Xiong YL 7; Wall W 4; White DJ 5; Zhong R*1,3,4,5; zzhong@uwo.ca
	2006
发表期刊	TRANSPLANTATION
ISSN	0041-1337
卷号	81 期号:2 页码:273-283
合作性质	其它
摘要	Background. The present study was undertaken to determine the role of preformed and induced anti-non-Gal antibodies in the rejection of hDAF pig-to-baboon kidney xenotransplants after anti-Gal antibody neutralization therapy. Methods. Seven baboons received life-supporting kidney transplants from hDAF transgenic pigs. Anti-Gal antibodies were neutralized by GAS914 or TPC (a Gal PEG glycoconjugate polymer). Group 1 (n=5) under-went a conventional immunosuppressive therapy with FK506, rabbit anti-thymocyte serum/immunoglobulin, mycophenolate mofetil, and steroids. Group 2 (n=2) received an anti-humoral immunity regimen with LF15-0195, Rituxan and cobra venom factor in addition to ATG, FK506 and steroids. Levels of anti-non-Gal antibodies and their mediated complement-dependent cytotoxic activities (CDC) were detected by flow cytometry using Gal knockout (k/o) pig lymphocytes (LC) or endothelial cells (EC) as targets. Results. Continuous infusion of GAS914/TPC significantly reduced anti-Gal antibodies. In Group 1, four of five baboons developed severe acute humoral xenograft rejection (AHXR) and the rejection was associated with either a high level of preformed anti-non-Gal IgG or a marked elevation in induced anti-non-Gal IgG and IgM. Sera collected at the time of AHXR had a high level of CDC to porcine LC/EC from Gal k/o animals. The intensive anti-humoral therapy in Group 2 completely inhibited both anti-Gal and non-Gal antibody production and prevented AHXR. However, this therapy was not well tolerated by the baboons. Conclusion. In a pig-to-baboon kidney transplant model, both preformed and induced anti-non-Gal antibodies are strongly associated with the pathogenesis of AHXR when anti-Gal antibodies are neutralized.
关键词	Xenotransplantation Kidney Pig Baboon Gal
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收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/2819
专题	其他
通讯作者	zzhong@uwo.ca
作者单位	1.Univ Western Ontario, Dept Surg, London, ON N6A 3K7, Canada 2.Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Organ Transplantat, Wuhan, Peoples R China 3.Univ Western Ontario, Dept Pathol, London, England 4.London Hlth Sci Ctr, Multiorgan Transplant Program, London, ON, Canada 5.Robarts Res Inst, Transplant Grp, London, ON, Canada 6.Univ Toronto, Dept Med, Toronto, ON, Canada;Univ Hlth Network, Toronto, ON, Canada 7.Chinese Acad Sci, Kunming Inst Zool, Anim Toxinol Lab, Kunming, Peoples R China
推荐引用方式 GB/T 7714	Chen G,Sun HT,Yang HJ,et al. The role of anti-non-Gal antibodies in the development of acute humoral xenograft rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal antibody neutralization therapy[J]. TRANSPLANTATION,2006,81(2):273-283.
APA	Chen G.,Sun HT.,Yang HJ.,Kubelik D.,Garcia B.,...&zzhong@uwo.ca.(2006).The role of anti-non-Gal antibodies in the development of acute humoral xenograft rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal antibody neutralization therapy.TRANSPLANTATION,81(2),273-283.
MLA	Chen G,et al."The role of anti-non-Gal antibodies in the development of acute humoral xenograft rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal antibody neutralization therapy".TRANSPLANTATION 81.2(2006):273-283.

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