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Classification of Rejection in Host Recipients in Xenotransplantation

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Glycoimmunology in Xenotransplantation
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Abstract

Glycome difference between human and non-human species is the most basic concept as a main barrier of xenotransplantation. Determination of xenogeneic carbohydrate antigens different from interspecies and different species is the first and the crucial step because cell surfaced carbohydrates are biosynthesized by diverse and various glycosyltransferases. They are bound by preformed natural Abs or de novo biosynthesized Abs. They are subjects of the reaction to incompatible blood products, tissues, and organs. In the vascular endothelium, the transplanted endothelial cells of the donor organ are the first lines and contacting sites with the host recipient’s blood in organ transplantation. In vascular endothelium, endothelial cells regularly express their self-protecting substances in terms of anti-inflammatory molecule and anticoagulative agents on cell surfaces, which are naturally crucial for the blood anticoagulation and for homeostatic self-protection. Genetically distinct differences are well known between the donors and host recipients, which are the basic causing factors for the rejection during cell, tissue, and organ xenotransplantation in the recipient immune system, consequently resulting in complete failure of the transplantation. Several biological incompatibilities between pigs and humans are the fundamental basis to prevent clinical xenotransplantation. Indeed, pig xenogeneic organs are immunologically rejected by the immune system of human by the most basic AMR. Xenoantigenic grafts are the major subject of immune rejections in mode of species- and tissue-specific carbohydrate antigens.

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References

  1. Rydberg L, Molne J, Strokan V, et al. Histo-blood group A antigen expression in pig kidneys–implication for ABO incompatible pig-to-human xenotransplantation. Scand J Urol Nephrol. 2001;35:54–62.

    Article  CAS  PubMed  Google Scholar 

  2. Kuwaki K, Tseng Y-L, Dor FJMF, et al. Heart transplantation in baboons using [alpha]1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med. 2005;11:29.

    Article  CAS  PubMed  Google Scholar 

  3. Yamada K, Yazawa K, Shimizu A, et al. Marked prolongation of porcine renal xenograft survival in baboons through the use of [alpha]1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med. 2005;11:32.

    Article  CAS  PubMed  Google Scholar 

  4. Siegel JB, Grey ST, Lesnikoski B-A, et al. Xenogeneic endothelial cells activate human prothrombin. Transplantation. 1997;64:888.

    Article  CAS  PubMed  Google Scholar 

  5. Kopp CW, Siegel JB, Hancock WW, et al. Effect of porcine endothelial tissue factor pathway inhibitor on human coagulation factors. Transplantation. 1997;63:749.

    Article  CAS  PubMed  Google Scholar 

  6. Yamada K, Yazawa K, Shimizu A, Iwanaga T, Hisashi Y, Nuhn M, O’Malley P, Nobori S, Vagefi PA, Patience C, Fishman J, Cooper DK, Hawley RJ, Greenstein J, Schuurman HJ, Awwad M, Sykes M, Sachs DH. Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med. 2005;11(1):32–4.

    Article  CAS  PubMed  Google Scholar 

  7. Kuwaki K, Tseng YL, Dor FL, Shimizu A, Houser SL, Sanderson TM, Lancos CJ, Prabharasuth DD, Cheng J, Moran K, Hisashi Y, Mueller N, Yamada K, Greenstein JL, Hawley RJ, Patience C, Awwad M, Fishman JA, Robson SC, Schuurman HJ, Sachs DH, Cooper DK. Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med. 2005;11(1):29–31.

    Article  CAS  PubMed  Google Scholar 

  8. Kiernan K, Harnden I, Gunthart M, Gregory C, Meisner J, Kearns-Jonker M. The anti-non-gal xenoantibody response to xenoantigens on gal knockout pig cells is encoded by a restricted number of germline progenitors. Am J Transplant. 2008;8(9):1829–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lam TT, Paniagua R, Shivaram G, Schuurman HJ, Borie DC, Morris RE. Anti-non-Gal porcine endothelial cell antibodies in acute humoral xenograft rejection of hDAF-transgenic porcine hearts in cynomolgus monkeys. Xenotransplantation. 2004;11(6):531–5.

    Article  PubMed  Google Scholar 

  10. Ramirez P, Montoya MJ, Rios A, Garcia Palenciano C, Majado M, Chavez R, et al. Prevention of hyperacute rejection in a model of orthotopic liver xenotransplantation from pig to baboon using polytransgenic pig livers (CD55, CD59, and H-transferase). Transplant Proc. 2005;37(9):4103–6.

    Article  CAS  PubMed  Google Scholar 

  11. Chen G, Sun H, Yang H, Kubelik D, Garcia B, Luo Y, 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. 2006;81(2):273–83.

    Article  CAS  PubMed  Google Scholar 

  12. Nozawa S, Xing P-X, Wu GD, Gochi E, Kearns-Jonker M, Swensson J, et al. Characteristics of immunoglobulin gene usage of the xenoantibody binding to Gal-α(1,3) Gal target antigens in the Gal knockout mouse. Transplantation. 2001;72:147–55.

    Article  CAS  PubMed  Google Scholar 

  13. Kearns-Jonker M, Fraiman M, Chu W, Gochi E, Michel J, Wu G–D, Cramer DV. Xenoantibodies to pig endothelium are expressed in germline configuration and share a conserved immunoglobulin VH gene structure with antibodies to common infectious agents. Transplantation. 1998;65:1515–9.

    Article  CAS  PubMed  Google Scholar 

  14. Kearns-Jonker M, Swensson J, Ghiuzeli C, Chu W, Osame Y, Baquerizo A, Demetriou A, Cramer DV. The human antibody response to porcine xenoantigens is encoded by IGHV3-11 and IGHV3-74 IgVH germline progenitors. J Immunol. 1999;163:4399–412.

    Article  CAS  PubMed  Google Scholar 

  15. Kleihauer A, Gregory CR, Borie D, Kyles AE, Shulkin IS, Patanwala I, Zahorsky-Reeves J, Starnes VA, Mullen Y, Todorov I, Kearns-Jonker M. Identification of the VH genes encoding xenoantibodies in non-immunosuppressed rhesus monkeys. Immunology. 2005;116:89–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zahorsky-Reeves J, Gregory C, Cramer DV, Kyles AE, Borie DC, Christe KL, Starnes VA, Kearns-Jonker M. Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes. BMC Immunol. 2006;7(1):3.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nguyen H, Sato N, MacKenzie C, Brade L, Kosma P, Brade H, Evans S, Oliva B, Bates P, Querol E, Aviles F, Sternberg M. Automated classification of antibody complementarity determining region 3 of the heavy chain (H3) loops into canonical forms and its application to protein structure prediction. J Mol Biol. 1998;279(5):1193–210.

    Article  Google Scholar 

  18. Cozzi E, White DJ. The generation of transgenic pigs as potential organ donors for humans. Nat Med. 1995;1(9):964–6.

    Article  CAS  PubMed  Google Scholar 

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Kim, CH. (2024). Classification of Rejection in Host Recipients in Xenotransplantation. In: Glycoimmunology in Xenotransplantation. Springer, Singapore. https://doi.org/10.1007/978-981-99-7691-1_9

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