NDLI: Acute rejection after swine leukocyte antigen-matched kidney allo-transplantation in cloned miniature pigs with different mitochondrial DNA-encoded minor histocompatibility antigen.

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Acute rejection after swine leukocyte antigen-matched kidney allo-transplantation in cloned miniature pigs with different mitochondrial DNA-encoded minor histocompatibility antigen.

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Acute rejection after swine leukocyte antigen-matched kidney allo-transplantation in cloned miniature pigs with different mitochondrial DNA-encoded minor histocompatibility antigen.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kwak, H-H Park, K-M Teotia, P. K. Lee, G-S Lee, E-S Hong, S-H Yang, S-R Park, S-M Ahn, C. Park, C-K Lee, K-W Woo, H-M
Description	Country affiliation: South Korea Author Affiliation: Kwak HH ( Stem Cell Institute, Kangwon National University, Chuncheon, South Korea.)
Abstract	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)-1ß 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.
File Format	HTM / HTML
ISSN	00411345
Issue Number	5
Volume Number	45
e-ISSN	18732623
Journal	Transplantation Proceedings
Language	English
Publisher	Elsevier
Publisher Date	2013-06-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Transplantation__semicolon__medicine Dna, Mitochondrial Genetics Graft Rejection Immunology Kidney Transplantation Minor Histocompatibility Antigens Animals Base Sequence Dna Primers Histocompatibility Testing Polymerase Chain Reaction Swine Swine, Miniature Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Transplantation Surgery

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