Elucidation of amyloid-transmission in iatrogenic FAP associated with domino liver transplantation
Project/Area Number |
17K08739
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Human pathology
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Research Institution | Shinshu University |
Principal Investigator |
YAZAKI MASAHIDE 信州大学, 学術研究院保健学系, 教授 (70372513)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | アミロイドーシス / トランスサイレチン / 家族性アミロイドポリニューロパチー / ドミノ肝移植 / レーザーマイクロダイセクション / ドミノ肝移植関連アミロイドーシス / アミロイド伝播 / 移植医療 / 医原性アミロイドーシス |
Outline of Final Research Achievements |
The most serious issue in domino liver transplantation using graft liver from patients with familial amyloid polyneuropathy (FAP) is transmission of transthyretin-related amyloidosis to recipients. In this study, to elucidate pathophysiology of early-stage amyloid deposits in domino related FAP, we carried out pathological and biochemical evaluations on gastroduodenal amyloid of 8 domino recipients. Deposited amyloid was extracted using laser micro-dissection system and analyzed by tandem mass spectrometry (LC-MS/MS). In most patients, variant TTR was main component of early-stage amyloid proteins. By detailed pathological re-examination, it was revealed that early stage amyloid deposition may often be overlooked on routine histopathological examinations.
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Academic Significance and Societal Importance of the Research Achievements |
本研究の学術的意義は、従来のアミロイド抽出法では解析できなかったドミノ移植関連アミロイドーシスの沈着超早期段階でのアミロイド蛋白とその付随蛋白を、LMDを用いて解析し、経時的なアミロイド沈着動態を早期段階から明らかにしたこと、また予想通りの結果であったが、変異型TTRがまず最初に核としてアミロイドを形成する点を明らかにしたことである。FAP患者や、老化に伴い野生型TTRが沈着する老人性全身性アミロイドーシス(SSA)では、発症前に組織生検をする機会は皆無であり、実際のヒト組織における沈着(超)早期段階での解析では、本研究は世界初となる。
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils provide insights into the involvement of lipoproteins in the pathology of amyloidosis2018
Author(s)
Miyahara H, Sawashita J, Ishikawa E, Yang M, Ding X, Liu Y, Hachiya N, Kametani F, Yazaki M, Mori M, Higuchi K
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Journal Title
J Proteomics
Volume: 172
Pages: 111-121
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Nationwide Survey of 741 Patients with Systemic Amyloid Light-chain Amyloidosis in Japan2018
Author(s)
Shimazaki C, Hata H, Iida S, Ueda M, Katoh N, Sekijima Y, Ikeda S, Yazaki M, Fukushima W, Ando Y
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Journal Title
Internal Medicine
Volume: 57
Issue: 2
Pages: 181-187
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed / Open Access
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