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IgG, but not IgM, mediates hyperacute rejection in hepatic xenografting

IgG, but not IgM, mediates hyperacute rejection in hepatic xenografting We reported previously that no classical features of hyperacute rejection (HAR) could be found in liver grafts in the guinea‐pig (GP)‐to‐rat model and that recipients died shortly after transplantation of non‐immunologic causes. Thus, the GP‐to‐rat model is not suitable for studying the mechanisms of discordant liver xenograft rejection. In the hamster to rat model, long‐term survival of a liver graft is possible, but extremely low levels of xenoreactive natural antibodies are present. To mimic a discordant situation with pre‐formed IgM and IgG antibodies, we sensitized rats 1 or 5 weeks before grafting. Specific anti‐hamster IgM antibodies were found in recipients sensitized at week –1 but not week –5. Anti‐hamster IgG was present in all recipients, albeit considerably higher in animals sensitized 5 weeks before grafting. In these two models, we examined the mechanism of HAR of liver grafts and compared this with heart xenografts. Control heart and liver grafts were rejected 4 and 7 days after transplantation respectively. Liver grafts in recipients sensitized at week –5 showed venous congestion and bleeding after reperfusion, indicating HAR, however this was not observed after sensitization at week –1. This surprising finding was confirmed by histology. Massive extravasation, edema, and acute liver cell degradation were noticed in grafts subjected to HAR. Liver grafts of recipients sensitized at week –1 showed only minimal changes. Heart grafts were rejected hyperacutely in both sensitization models. IgG antibodies could be detected on liver grafts in the group sensitized at week –5 but not in the group sensitized at week –1. Minimal IgM depositions were found on liver grafts of animals sensitized 1 week before grafting. Rejected heart grafts from similar sensitization groups showed identical antibody depositions; only IgM depositions were massive. Complement depositions were found in all groups. These results indicate that IgG, but not IgM, mediates HAR in hepatic xenografting. Such a predominance of IgG over IgM does not exist for heart grafts. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Xenotransplantation Wiley

IgG, but not IgM, mediates hyperacute rejection in hepatic xenografting

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References (43)

Publisher
Wiley
Copyright
Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0908-665X
eISSN
1399-3089
DOI
10.1034/j.1399-3089.1999.00010.x
Publisher site
See Article on Publisher Site

Abstract

We reported previously that no classical features of hyperacute rejection (HAR) could be found in liver grafts in the guinea‐pig (GP)‐to‐rat model and that recipients died shortly after transplantation of non‐immunologic causes. Thus, the GP‐to‐rat model is not suitable for studying the mechanisms of discordant liver xenograft rejection. In the hamster to rat model, long‐term survival of a liver graft is possible, but extremely low levels of xenoreactive natural antibodies are present. To mimic a discordant situation with pre‐formed IgM and IgG antibodies, we sensitized rats 1 or 5 weeks before grafting. Specific anti‐hamster IgM antibodies were found in recipients sensitized at week –1 but not week –5. Anti‐hamster IgG was present in all recipients, albeit considerably higher in animals sensitized 5 weeks before grafting. In these two models, we examined the mechanism of HAR of liver grafts and compared this with heart xenografts. Control heart and liver grafts were rejected 4 and 7 days after transplantation respectively. Liver grafts in recipients sensitized at week –5 showed venous congestion and bleeding after reperfusion, indicating HAR, however this was not observed after sensitization at week –1. This surprising finding was confirmed by histology. Massive extravasation, edema, and acute liver cell degradation were noticed in grafts subjected to HAR. Liver grafts of recipients sensitized at week –1 showed only minimal changes. Heart grafts were rejected hyperacutely in both sensitization models. IgG antibodies could be detected on liver grafts in the group sensitized at week –5 but not in the group sensitized at week –1. Minimal IgM depositions were found on liver grafts of animals sensitized 1 week before grafting. Rejected heart grafts from similar sensitization groups showed identical antibody depositions; only IgM depositions were massive. Complement depositions were found in all groups. These results indicate that IgG, but not IgM, mediates HAR in hepatic xenografting. Such a predominance of IgG over IgM does not exist for heart grafts.

Journal

Xenotransplantation – Wiley

Published: May 1, 1999

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