The influence of baseline expression of human decay accelerating factor transgene on graft survival and acute humoral xenograft rejection.
BACKGROUND
Transgenic pigs expressing human decay accelerating factor (hDAF) have been widely used as donors in various non-human primate transplant models. Despite the use of similar immunosuppressive protocols, there is marked variation in graft survival among centres. The present study was undertaken to determine whether the level of hDAF expression in the pig kidney correlates with the degree of rejection and duration of graft survival.


METHODS
hDAF transgenic pigs were provided from two suppliers: Guelph Imutran Centre (G) and Harlan Sprague Dawley (H). Following a bilateral nephrectomy, a single hDAF pig kidney was implanted in the baboon, which was subsequently treated with conventional immunosuppressive protocols. The pig's contralateral kidney was collected to provide baseline data. The severity of acute humoral xenograft rejection (AHXR) was graded as stage I-III. hDAF expression was measured using morphologic analysis comparing the contralateral and grafted kidneys at the endpoint.


RESULTS
Baseline hDAF expression in kidneys from pigs provided by supplier G was significantly higher than that from supplier H (P<0.01). Furthermore, the survival of baboons receiving grafts from G pigs was significantly longer than those receiving grafts from H pigs (P<0.05). In addition, reduction of hDAF expression at the endpoint was associated with a higher degree of AHXR. Severe apoptosis or necrosis was found in grafts with AHXR II-III.


CONCLUSIONS
Pig kidneys from different suppliers have variable baseline hDAF expression, which may have an influence on graft survival. Reduced expression of hDAF in the terminal graft was associated with the severity of rejection.
Sun
Hongtao
H
Department of Pathology, University of Western Ontario, and Multi-Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada.
Chen
Gang
G
Liu
Weihua
W
Kubelik
Dalibor
D
Yang
Hongji
H
White
David J
DJ
Zhong
Robert
R
Garcia
Bertha
B
D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D018958:CD55 Antigens / Q000235:genetics*; D016923:Cell Death; D004727:Endothelium / Q000503:physiopathology; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000503:physiopathology; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology*; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000276:immunology*; D010215:Papio; D012720:Severity of Illness Index; D013552:Swine; D019076:Transgenes; D014183:Transplantation, Heterologous
D018958:CD55 Antigens