| Project/Area Number |
17390347
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
KIUCHI Tetsuya Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (40303820)
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Hisami Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (60184321)
FUJIMOTO Yasuhiro University Hospital, Research Associate, 医学部附属病院, 助手 (80335281)
KAMEI Hideya University Hospital, Medical Staff, 医学部附属病院, 医員 (80422773)
HAGA Hironori Kyoto University, Graduate School of Medicine, Research Associate, 大学院医学研究科, 助手 (10252462)
NAKAMURA Sigeo Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (80180363)
山本 栄和 名古屋大学, 医学部附属病院, 医員 (10378101)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,700,000 (Direct Cost: ¥15,700,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2005: ¥13,300,000 (Direct Cost: ¥13,300,000)
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| Keywords | pediatric liver transplantation / autoimmune hepatitis / tissue crossmatch / rejection / anti-nuclear antibody / anti-smooth muscle antibody / immunoglobulin / chronic rejection |
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| Research Abstract |
Liver dysfunction accompanied by de novo serum auto-antibody was observed in 9 (19%) of 48 pediatric liver transplant patients followed for 27 months in median. There was no gender deviation and onset was 2-71 (median 27) months after transplantation. The patients received liver transplant at the age of 0.5-25.3 (median 13) years. Six patients developed anti-nuclear antibody (ANA), two anti-smooth muscle antibody, and two anti-LKM-1 antibody, two of whom was accompanied by increase of IgG. Graft histology was more or less compatible with acute rejection combined with interface hepatitis. All cases responded to corticosteroid and azathiopurine. This group combined with other children with similar symptoms were studied as posttransplant de novo autoimmune hepatitis (AIH).
To specify antigen-antibody reaction in de novo AIH, tissue crossmatch between sera at the onset or after treatment and graft liver tissue was done. Although some antigen-antibody reaction was observed on bile duct and portal and hepatic venous endothelium, similar reactions were occasionally observed in cases without de novo AIH. The extent or loci of the reaction varied. It is conjectured that de novo antibody production against graft liver led to the pathogenesis of the disease. A strong reaction on the biliary epithelium was observed in another case with ductopenic chronic rejection, in which identification, timing, and trigger of antibody production are under investigation.
Because some report regards de novoAIH as a type of chronic reject ion, the comparison with ductopenic rejection is full of implications. Although identification of antibodies specific to de novo AIH is under process, comparison between ductopenic chronic rejection and de novo AIH is expected to lead to the elucidation of the role of de novo antibody in pediatric liver transplantation and to the possibility that the difference of target antigen can discriminate the two distinct pathogenesis.
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