2016 Fiscal Year Final Research Report
Diversity analysis of antibody function and development of strategy to overcome antibody-mediate rejection: Establishment of pig model for ABO/HLA-incompatibility
| Project/Area Number |
15K15472
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Research Collaborator |
FUCHIMOTO Daiichiro
SUZUKI Shunichi
YAMAMOTO Takayuki
OKADA Manabu
TAKEDA Asami
HIRAMITSU Takahisa
KITAGAWA Hitoshi
IMAEDA Noriaki
HANEDA Masataka
HORIMI Kosei
MATSUOKA Yutaka
MAENAKA Akihiro
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | 移植・再生医療 / ABO血液型不適合 / HLA抗体 / 抗体陽性腎移植 / モデルブタ / 遺伝子 |
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| Outline of Final Research Achievements |
Control of antibody-mediated rejection caused by blood group ABO or HLA-incompatibility is essential for long-term graft survival after organ transplantation. Blood group A or B transferase and fucosyltransferase (FUT1) were transfected into two types of Duroc fibroblasts (non-A). We attempted to produce cloned pig expressing blood group A or B.
Subclass IgG4 and RNA interference were effective for reducing antibody-mediated, complement dependent cytotoxicity. Acute antibody-mediated rejection after ABO-incompatible renal transplantation was associated with pre-transplant IgG1,IgG2, IgG3 and C1q binding capacity. Microarray analysis using graft biopsy revealed that ABO-incompatibility could increase BACH1 gene and decrease reactive oxygen species. Anti-A/B antibody binding to endothelial cells induced the resistance to antibody-mediated, complement-dependent cytotoxicity due to downregulation of HLA-DR expression and upregulation of complement regulatory proteins (CD55 and CD59).
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| Free Research Field |
移植免疫、移植外科
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