2002 Fiscal Year Final Research Report Summary
Molecular control of humoral rejection in organ transplantation
| Project/Area Number |
13671225
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
YOKOYAMA Istuo Nagoya University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (60240206)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAO Akimasa Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70167542)
NAGASAKA Takaharu Nagoya University, University Hospital Hedical Staff, 医学部附属病院, 医員
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| Project Period (FY) |
2001 – 2002
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| Keywords | organ transplantation / humoral rejection / antigen-antibody reaction / ABO blood group / α-galactose antigen / major histocompatibility complex antigen / endo-β-galactosidase C / genetic modification |
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| Research Abstract |
The purpose of this study was (i) to analyze the mechanisms of antibody-mediated rejection after organ transplantation with preformed anti-donor antibodies such as ABO-incompatible, crossmatch-positive and xeno-transplantation and (ii) to find the strategy to control such rejections molecularly.
Anti-donor antibody levels after clinical liver and kidney ABO-incompatible and crossmatch-positive transplantation were suppressed to 30-50% of pre-treatment level. Analysis of antigen expression is also important to elucidate the nature of rejection further in detail.
We established the pig allo-transplantation model which would certainly cause the production of anti-donor antibodies (most likely anti-SLA), resulting in humoral rejection within a week.
For successful xenotransplantation, we attempted the elimination of alpha-Gal antigens expressed in pig organs using endo-beta-galactosidaseC (EndoGalC). In vivo infusion of recombinant EndoGalC succeeded in removing alpha-Gal expression in pig organs without major adverse effect. Pig to baboon transplantation using EndoGalC-treated kidney suppressed hyperacute rejection.
We are now trying to produce genetic engineered pig expressing EndoGalC for clinical application.
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