title: Acute rejection after swine leukocyte antigen-matched kidney allo-transplantation in cloned miniature pigs with different mitochondrial DNA-encoded minor histocompatibility antigen.
abstract: BACKGROUND
  Graft rejection remains a major cause of morbidity and mortality following renal transplantation. One of the main determinants of success after renal transplantation is histocompatibility between donor and recipient. Most of the research on this topic has addressed human leukocyte antigen (HLA), but the roles played by minor histocompatibility antigens (mHAgs), such as mitochondrially transmitted antigens, are poorly understood. In this study, we evaluated immune responses induced by minor antigens originating from mitochondrial DNA (mtDNA) in a large animal model.
  
  
  METHODS
  To characterize whole swine leukocyte antigen (SLA) allele in 8 cloned pigs, we performed SLA genotyping for SLA-1, SLA-2, SLA-3, SLA-DQB1, and SLA-DRB1 as well as the hypervariable region 1 (HV1) of mtDNA. Renal transplantation was performed using SLA-matched pigs with different mtDNA as well as SLA-mismatched cloned animals. Cytokine profiling was performed by incubating peripheral leukocytes with cellular components from SLA-matched different mtDNA and SLA-mismatched cells to evaluate mtDNA-mediated immune response.
  
  
  RESULTS
  SLA types were confirmed to be identical, but mtDNA sequences of HV1 varied among cloned pigs. Rejection episodes in the SLA-matched group with different mtDNA were similar to those in the SLA-mismatched group; that is, plasma creatinine and BUN levels were increased and mononuclear cell infiltration was observed in perivascular regions in the matched and SLA-mismatched groups. Furthermore, in vitro studies showed interleukin (IL)-1β expression to be elevated in SLA-matched and SLA-mismatched groups.
  
  
  CONCLUSIONS
  Cloned pigs are a useful preclinical model to evaluate the immunogenicity of mtDNA encoding minor antigens. The mtDNA originating from nongenomic DNA induced cell-mediated immune rejection after kidney transplantation.
authors.affiliation: Stem Cell Institute, Kangwon National University, Chuncheon, South Korea.
authors.forename: H-H
authors.initials: HH
authors.lastname: Kwak
authors.forename: K-M
authors.initials: KM
authors.lastname: Park
authors.forename: P K
authors.initials: PK
authors.lastname: Teotia
authors.forename: G-S
authors.initials: GS
authors.lastname: Lee
authors.forename: E-S
authors.initials: ES
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Hong
authors.forename: S-R
authors.initials: SR
authors.lastname: Yang
authors.forename: S-M
authors.initials: SM
authors.lastname: Park
authors.forename: C
authors.initials: C
authors.lastname: Ahn
authors.forename: C-K
authors.initials: CK
authors.lastname: Park
authors.forename: K-W
authors.initials: KW
authors.lastname: Lee
authors.forename: H-M
authors.initials: HM
authors.lastname: Woo
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D006084:Graft Rejection / Q000276:immunology*; D006650:Histocompatibility Testing; D016030:Kidney Transplantation; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013552:Swine; D013556:Swine, Miniature
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D015778:Minor Histocompatibility Antigens