PMID- 23769038
OWN - NLM
STAT- MEDLINE
DCOM- 20140127
LR  - 20130617
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 45
IP  - 5
DP  - 2013 Jun
TI  - Acute rejection after swine leukocyte antigen-matched kidney allo-transplantation 
      in cloned miniature pigs with different mitochondrial DNA-encoded minor 
      histocompatibility antigen.
PG  - 1754-60
LID - S0041-1345(13)00317-5 [pii]
LID - 10.1016/j.transproceed.2013.02.103 [doi]
AB  - INTRODUCTION: 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)-1beta expression to be elevated in SLA-matched and SLA-mismatched 
      groups. CONCLUSION: 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.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Kwak, H-H
AU  - Kwak HH
AD  - Stem Cell Institute, Kangwon National University, Chuncheon, South Korea.
FAU - Park, K-M
AU  - Park KM
FAU - Teotia, P K
AU  - Teotia PK
FAU - Lee, G-S
AU  - Lee GS
FAU - Lee, E-S
AU  - Lee ES
FAU - Hong, S-H
AU  - Hong SH
FAU - Yang, S-R
AU  - Yang SR
FAU - Park, S-M
AU  - Park SM
FAU - Ahn, C
AU  - Ahn C
FAU - Park, C-K
AU  - Park CK
FAU - Lee, K-W
AU  - Lee KW
FAU - Woo, H-M
AU  - Woo HM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Minor Histocompatibility Antigens)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers
MH  - DNA, Mitochondrial/*genetics
MH  - Graft Rejection/*immunology
MH  - Histocompatibility Testing
MH  - *Kidney Transplantation
MH  - Minor Histocompatibility Antigens/*genetics
MH  - Polymerase Chain Reaction
MH  - Swine
MH  - Swine, Miniature
EDAT- 2013/06/19 06:00
MHDA- 2014/01/28 06:00
CRDT- 2013/06/18 06:00
PHST- 2012/12/14 00:00 [received]
PHST- 2013/02/11 00:00 [revised]
PHST- 2013/02/27 00:00 [accepted]
PHST- 2013/06/18 06:00 [entrez]
PHST- 2013/06/19 06:00 [pubmed]
PHST- 2014/01/28 06:00 [medline]
AID - S0041-1345(13)00317-5 [pii]
AID - 10.1016/j.transproceed.2013.02.103 [doi]
PST - ppublish
SO  - Transplant Proc. 2013 Jun;45(5):1754-60. doi: 10.1016/j.transproceed.2013.02.103.