A model of acute renal allograft rejection in outbred Yorkshire piglets

Randi Lassiter, Youli Wang, Xuexiu Fang, Matt Winn, Arina Ghaffari, Chak Sum Ho, Sandra W Helman, Ryan Jajosky, Daniel T Kleven, Norris Stanley Nahman, Todd David Merchen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)40-46
Number of pages7
JournalTransplant Immunology
Volume42
DOIs
StatePublished - Jun 1 2017

Keywords

  • Genotyping
  • Outbred pigs
  • Porcine transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation

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