TY - JOUR
T1 - A model of acute renal allograft rejection in outbred Yorkshire piglets
AU - Lassiter, Randi
AU - Wang, Youli
AU - Fang, Xuexiu
AU - Winn, Matt
AU - Ghaffari, Arina
AU - Ho, Chak Sum
AU - Helman, Sandra W
AU - Jajosky, Ryan
AU - Kleven, Daniel T
AU - Nahman, Norris Stanley
AU - Merchen, Todd David
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Pigs represent a desirable animal model for the study of rejection in kidney transplantation with inbred Yucatan miniature swine (YMS) the most commonly studied strain due to well defined swine leukocyte antigen (SLA) genotypes. However, limitations to YMS may include cost and availability. Outbred Yorkshire pigs are widely available and significantly cheaper than YMS. Recent advances in SLA genotyping have allowed its application to outbred strains. On this basis, we theorized that Yorkshire pigs would be a viable alternative to YMS for the study of rejection in kidney transplantation. To address this question, we performed auto (Auto) and allotransplants (Allo) in 24 Yorkshire pigs, and assessed SLA genotypes and acute rejection after 72 h. At sacrifice, and when compared to autotransplants, allotransplants had significant elevations in serum creatinine (8.4 ± 1.3 vs 2.8 ± 2.0 mg/dL for Allo vs autotransplants, respectively) and BUN (61 ± 9 vs 19.2 ± 15 mg/dL for Allo vs autotransplants, respectively). Warm ischemia times between the two groups did not differ (24 ± 2.3 vs 26.4 ± 1.4 min for Auto vs Allo, respectively). There were 16 distinct SLA haplotypes identified from pigs undergoing allotransplantion, no matched donor-recipient pairs, and all allografts demonstrated rejection. Type IIA cellular rejection (Banff) was the most common. One allograft demonstrated hyperacute rejection due a blood group incompatibility. Histologically, the expression of regulatory Tcells and dendritic cells was increased in allografts. These data suggest that Yorkshire pigs may be a useful model for the study of acute rejection in experimental kidney transplantation.
AB - Pigs represent a desirable animal model for the study of rejection in kidney transplantation with inbred Yucatan miniature swine (YMS) the most commonly studied strain due to well defined swine leukocyte antigen (SLA) genotypes. However, limitations to YMS may include cost and availability. Outbred Yorkshire pigs are widely available and significantly cheaper than YMS. Recent advances in SLA genotyping have allowed its application to outbred strains. On this basis, we theorized that Yorkshire pigs would be a viable alternative to YMS for the study of rejection in kidney transplantation. To address this question, we performed auto (Auto) and allotransplants (Allo) in 24 Yorkshire pigs, and assessed SLA genotypes and acute rejection after 72 h. At sacrifice, and when compared to autotransplants, allotransplants had significant elevations in serum creatinine (8.4 ± 1.3 vs 2.8 ± 2.0 mg/dL for Allo vs autotransplants, respectively) and BUN (61 ± 9 vs 19.2 ± 15 mg/dL for Allo vs autotransplants, respectively). Warm ischemia times between the two groups did not differ (24 ± 2.3 vs 26.4 ± 1.4 min for Auto vs Allo, respectively). There were 16 distinct SLA haplotypes identified from pigs undergoing allotransplantion, no matched donor-recipient pairs, and all allografts demonstrated rejection. Type IIA cellular rejection (Banff) was the most common. One allograft demonstrated hyperacute rejection due a blood group incompatibility. Histologically, the expression of regulatory Tcells and dendritic cells was increased in allografts. These data suggest that Yorkshire pigs may be a useful model for the study of acute rejection in experimental kidney transplantation.
KW - Genotyping
KW - Outbred pigs
KW - Porcine transplantation
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U2 - 10.1016/j.trim.2017.05.001
DO - 10.1016/j.trim.2017.05.001
M3 - Article
C2 - 28495618
AN - SCOPUS:85019115054
SN - 0966-3274
VL - 42
SP - 40
EP - 46
JO - Transplant Immunology
JF - Transplant Immunology
ER -