title: IgG, but not IgM, mediates hyperacute rejection in hepatic xenografting.
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.
authors.affiliation: Department of Surgery, Erasmus University Rotterdam, The Netherlands.
authors.forename: E O
authors.initials: EO
authors.lastname: Schraa
authors.forename: H B
authors.initials: HB
authors.lastname: Stockmann
authors.forename: A J
authors.initials: AJ
authors.lastname: Broekhuizen
authors.forename: M
authors.initials: M
authors.lastname: Scheringa
authors.forename: H J
authors.initials: HJ
authors.lastname: Schuurman
authors.forename: R L
authors.initials: RL
authors.lastname: Marquet
authors.forename: J N
authors.initials: JN
authors.lastname: IJzermans
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology; D000918:Antibody Specificity; D006224:Cricetinae; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006168:Guinea Pigs; D016027:Heart Transplantation; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D016031:Liver Transplantation; D008647:Mesocricetus; D051381:Rats; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
chemical_list: D000910:Antibodies, Heterophile; D007074:Immunoglobulin G; D007075:Immunoglobulin M