Incidence of hyperacute rejection in pig-to-primate transplantation using organs from hDAF-transgenic donors.
BACKGROUND
Cynomolgus monkeys or baboons received under immunosuppression kidney or heart grafts from pigs transgenic for human decay-accelerating factor (hDAF) or from control pigs. Hyperacute rejection (HAR) is often difficult to differentiate from nonimmunological causes of organ or recipient dysfunction (NIC), and therefore, a thorough pathology review of all cases with 0-4 days survival (inclusive) was conducted.


METHODS
Pathology slides were blinded and together with limited clinical data reviewed by two pathologists. After unblinding, data were compared with the original diagnosis made during the course of the program, and a final diagnosis was reached considering the complete clinical dataset.


RESULTS
Life-supporting kidney transplantation was performed in 245 cynomolgus monkeys (234 hDAF, 11 controls), of which 102 cases had 0-4 day survival. None of the hDAF cases showed HAR, whereas this occurred in 27% of controls (P<10-6). Heterotopic heart transplantation was performed in 65 monkeys (57 hDAF, 8 controls), of which 41 cases had 0-4 day survival. HAR was observed in 7% of hDAF cases and in 57% of controls (P=0.002). Heterotopic heart transplantation in baboons was performed in 33 animals (28 hDAF, 5 controls), of which 15 cases had 0-4 day survival. HAR was observed in 11% of hDAF cases and in 20% of controls. Sixteen baboons were subjected to orthotopic heart transplantation, all from hDAF donors, out of which eight survived 0-4 days. The incidence of HAR was 6%.


CONCLUSIONS
In the largest series of pig-to-primate solid organ transplants performed thus far, the presence of the hDAF transgene fully prevents HAR of cynomolgus monkey kidney transplants and partially inhibits HAR of heart grafts in cynomolgus monkeys or baboons. The incidence of HAR in control grafts is significantly higher.
Schuurman
Henk-Jan
HJ
Imutran Ltd (A Novartis Pharma AG Company), Cambridge, United Kingdom. henk.schuurman@immergebt.com.
Pino-Chavez
Gilda
G
Phillips
M James
MJ
Thomas
Lucy
L
White
David J G
DJ
Cozzi
Emanuele
E
D000818:Animals; D030801:Animals, Genetically Modified; D018958:CD55 Antigens / Q000502:physiology*; D006084:Graft Rejection / Q000453:epidemiology*; D006801:Humans; D007165:Immunosuppression Therapy; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology*; D008252:Macaca fascicularis; D010215:Papio; D012189:Retrospective Studies; D013552:Swine; D014019:Tissue Donors; D014183:Transplantation, Heterologous / Q000276:immunology*
D018958:CD55 Antigens