Target Antigen of Hyperacute Rejection in PigtoHuman Xenotransplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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Laboratory of Transplant Engineer and Immunology, West China Hospital， Sichuan University, Chengdu 610041, China;

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Keywords：

Xenotransplantation; Pig to human xenotransplantation; αGal; Hyperacute rejection

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ObjectiveTo investigate the aim antigen coursing the hyperacute rejection of xenotransplantation. MethodsDocuments about hyperacute rejection in xenotransplantation were reviewed and summarized in detail. ResultsPig is thought to be one of the ideal donors of xenotransplantation, but the major obstacle is hyperacute rejection mediated by complement that is activated though human serum. αGal is recognized as the major antigen and its expression is controlled by α1,3 galactosyltransferase. Immunoabsorption of preexsisted antibody, enzymatic digestion of αGal, knockout αGT gene and transgenic technology have been used to solve this problem. Even so, there remain other antigens which can combine with natural antibodies in human serum, such as, 40×103 molecule in erythrocyte, 210×103, 105×103 and 50×103 antigen in pig embryo brain cell, etc. Conclusion αGal is the major antigen which course the hyperacute rejection. Besides αGal, many nonalphagal need further investigation.

Citation： ZENG Lingyu,LI Youping. Target Antigen of Hyperacute Rejection in PigtoHuman Xenotransplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2003, 10(4): 422-425. doi: Copy

1.	12Sumitran S， Liu J, Czech KA， et al.Human natural antibodies cytotoxic to pig embryonic brain cells recognize novel nonGal apha 1, 3 Galbased xenoantigens [J]. Exp Neurol, 1999; 159(2)∶347.
2.	李涛，李幼平, 杨志明. 猪到人异种移植抗原与移植免疫研究[J].中国修复重建外科杂志，1998； 12（1）∶42.
3.	Oriol R, Barthod F, Borgemer AM, et al.Monomorphic and polymorphic carbohydrate antigens on pig tissues: implications for organ xenotransplantation in the pigtohuman model [J]. Transpl Int, 1994； 7(6)∶405.
4.	McKenzie IF, Xing PX, Vaughan HA， et al. Distribution of the major xenoantigen [gal(alpha 13)gal] for pig to human xenografts [J]. 　Transpl Immunol, 1994; 2(2)∶81.
5.	Chae SJ, Kramer AD, Zhao Y， et al.Lack of variation in alpha Gal expression on lymphocytes in miniature swine of different genotypes [J]. Xenotransplantation, 1999; 6(1)∶43.
6.	Neethling FA, Cooper DK. Serum cytotoxicity to pigcells and antialpha Gal antibody level and specificity in humans and baboons [J]. Transplantation, 1999; 67(5)∶658.
7.	Stone KR, Ayala G, Goldstein J， et al. Porcine cartilage transplants in cynomolgus monkey. Ⅲ. transplantation of alphagalctosidasetreated porcine cartilage [J]. Transplantation, 1998; 65(12)∶1577.
8.	步宏，王华，魏启欧，等.　中国近交系猪到人异种移植靶抗原研究 [J]. 中国修复重建外科杂志， 2000； 14(2)∶115.
9.	McKenzie IF, Li YQ, Patton K， et al. A marine model of antibodymediated hyperacute rejection by galactosealpha(1,3) galactose antibodies in Gal o/o mice [J]. Transplantation, 1998; 66(6)∶754.
10.	Galili U, La Temple DC, Radic MZ. A sensitive assay for measuring alphaGal epitope expression on cells by a monoclonal antiGal antibody [J]. Transplantation, 1998; 65(8)∶1129.
11.	MaClaren L, Lee TD, Anderson D， et al. Variation in porcine red blood cell alphagalastosyl expression and agglutination by human serum [J]. Transplant Proc, 1998; 30(5)∶2468.
12.	Zhu A.Binding of human natural antibodies to nonalphaGal xenoantigens on porcine erythrocytes [J].Transplantation,2000; 69(11)∶2422.
13.	Gustavsson ML, Johnsson C, Albertsson P， et al. Characterization of Forssman and other antigen/antibody systems in vascularized mouse heart to rat xenotransplantation [J]. Scand J Immunol, 2001; 53(2)∶121.
14.	Squinto SP. Genetically modified animal organs, for human transplantation [J]. Word J Surg, 1997; 21(9)∶939.
15.	Ogawa H, Muramatsu H, Kobayashi T， et al. Molecular cloning of endobetagalactosidase C and its application in removing alphagalctosyl xenoantigen from blood vessels in the pig kidney [J]. J Biol Chem, 2000； 275(25)∶19368.
16.	Koma M, Miyagawa S, Honke K， et al.Reduction of the xenoantigen on glycosphingol lipids of swine endothelial cells by various glycosyltransferases [J]. Glycobiology, 2000; 10(7)∶745.
17.	Osman N, McKenzie IF, Ostenried K， et al. Combined transgenic expression of alphagalactosidase and alpha 1,2fucosyltransferase leads to optimal reduction in the major xenoeeitope Gal alpha(1,3)Gal [J]. Proc Natl Acad Sci USA， 1997; 94(26)∶ 14677.
18.	Carrington CA. Complement activation,its consequences, and blockade by gene transfer [J]. World J Surg, 1997; 21(9)∶907.
19.	Fisicaro N, Aminian A, Hinchliffe SJ， et al. The pig analogue of CD59 protects transgenic mouse hearts from injury by human complate [J]. Transplantation, 2000; 70(6)∶963.
20.	Cozzi E, Masroor S, Sion B， et al. Progress in xenotransplantation [J]. Clin Nephro, 2000; 53(4)∶13.
21.	Levy MF, Crippin J，Sutton S, et al. Liver allotransplantation after extracorporeal hepatic support with transgentic (hCD55/hCD59) porcine livers: clinical results and lack of pigtohuman transmission of the porcine endogenous retrovirus [J]. Transplantation, 2000; 69(2)∶272.
22.	Lai L, KolberSimonds D, Park KW， et al.Production of alpha1,3galactosytransferase knockout pigs by nuclear transfer cloning [J]. Science, 2002; 295(5557)∶1089.
23.	Dai Y, Vaught TD, Boone J， et al. Targeted disruption of the alpha1,3galactosyltransferase gene in cloned pigs [J]. Nat Biotechnol， 2002; 20(3)∶251.

1. 12Sumitran S， Liu J, Czech KA， et al.Human natural antibodies cytotoxic to pig embryonic brain cells recognize novel nonGal apha 1, 3 Galbased xenoantigens [J]. Exp Neurol, 1999; 159(2)∶347.
2. 李涛，李幼平, 杨志明. 猪到人异种移植抗原与移植免疫研究[J].中国修复重建外科杂志，1998； 12（1）∶42.
3. Oriol R, Barthod F, Borgemer AM, et al.Monomorphic and polymorphic carbohydrate antigens on pig tissues: implications for organ xenotransplantation in the pigtohuman model [J]. Transpl Int, 1994； 7(6)∶405.
4. McKenzie IF, Xing PX, Vaughan HA， et al. Distribution of the major xenoantigen [gal(alpha 13)gal] for pig to human xenografts [J]. 　Transpl Immunol, 1994; 2(2)∶81.
5. Chae SJ, Kramer AD, Zhao Y， et al.Lack of variation in alpha Gal expression on lymphocytes in miniature swine of different genotypes [J]. Xenotransplantation, 1999; 6(1)∶43.
6. Neethling FA, Cooper DK. Serum cytotoxicity to pigcells and antialpha Gal antibody level and specificity in humans and baboons [J]. Transplantation, 1999; 67(5)∶658.
7. Stone KR, Ayala G, Goldstein J， et al. Porcine cartilage transplants in cynomolgus monkey. Ⅲ. transplantation of alphagalctosidasetreated porcine cartilage [J]. Transplantation, 1998; 65(12)∶1577.
8. 步宏，王华，魏启欧，等.　中国近交系猪到人异种移植靶抗原研究 [J]. 中国修复重建外科杂志， 2000； 14(2)∶115.
9. McKenzie IF, Li YQ, Patton K， et al. A marine model of antibodymediated hyperacute rejection by galactosealpha(1,3) galactose antibodies in Gal o/o mice [J]. Transplantation, 1998; 66(6)∶754.
10. Galili U, La Temple DC, Radic MZ. A sensitive assay for measuring alphaGal epitope expression on cells by a monoclonal antiGal antibody [J]. Transplantation, 1998; 65(8)∶1129.
11. MaClaren L, Lee TD, Anderson D， et al. Variation in porcine red blood cell alphagalastosyl expression and agglutination by human serum [J]. Transplant Proc, 1998; 30(5)∶2468.
12. Zhu A.Binding of human natural antibodies to nonalphaGal xenoantigens on porcine erythrocytes [J].Transplantation,2000; 69(11)∶2422.
13. Gustavsson ML, Johnsson C, Albertsson P， et al. Characterization of Forssman and other antigen/antibody systems in vascularized mouse heart to rat xenotransplantation [J]. Scand J Immunol, 2001; 53(2)∶121.
14. Squinto SP. Genetically modified animal organs, for human transplantation [J]. Word J Surg, 1997; 21(9)∶939.
15. Ogawa H, Muramatsu H, Kobayashi T， et al. Molecular cloning of endobetagalactosidase C and its application in removing alphagalctosyl xenoantigen from blood vessels in the pig kidney [J]. J Biol Chem, 2000； 275(25)∶19368.
16. Koma M, Miyagawa S, Honke K， et al.Reduction of the xenoantigen on glycosphingol lipids of swine endothelial cells by various glycosyltransferases [J]. Glycobiology, 2000; 10(7)∶745.
17. Osman N, McKenzie IF, Ostenried K， et al. Combined transgenic expression of alphagalactosidase and alpha 1,2fucosyltransferase leads to optimal reduction in the major xenoeeitope Gal alpha(1,3)Gal [J]. Proc Natl Acad Sci USA， 1997; 94(26)∶ 14677.
18. Carrington CA. Complement activation,its consequences, and blockade by gene transfer [J]. World J Surg, 1997; 21(9)∶907.
19. Fisicaro N, Aminian A, Hinchliffe SJ， et al. The pig analogue of CD59 protects transgenic mouse hearts from injury by human complate [J]. Transplantation, 2000; 70(6)∶963.
20. Cozzi E, Masroor S, Sion B， et al. Progress in xenotransplantation [J]. Clin Nephro, 2000; 53(4)∶13.
21. Levy MF, Crippin J，Sutton S, et al. Liver allotransplantation after extracorporeal hepatic support with transgentic (hCD55/hCD59) porcine livers: clinical results and lack of pigtohuman transmission of the porcine endogenous retrovirus [J]. Transplantation, 2000; 69(2)∶272.
22. Lai L, KolberSimonds D, Park KW， et al.Production of alpha1,3galactosytransferase knockout pigs by nuclear transfer cloning [J]. Science, 2002; 295(5557)∶1089.
23. Dai Y, Vaught TD, Boone J， et al. Targeted disruption of the alpha1,3galactosyltransferase gene in cloned pigs [J]. Nat Biotechnol， 2002; 20(3)∶251.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Target Antigen of Hyperacute Rejection in PigtoHuman Xenotransplantation

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