Journal article
The pathological and biochemical identification of possible seed‐lesions of transmitted transthyretin amyloidosis after domino liver transplantation
The journal of pathology. Clinical research, Vol.2(2), pp.72-79
04/2016
DOI: 10.1002/cjp2.36
PMCID: PMC4907057
PMID: 27499917
Abstract
The most serious issue in domino liver transplantation (DLT) using liver grafts from patients with transthyretin (TTR)‐related familial amyloid polyneuropathy (FAP) is the development of iatrogenic transmitted amyloidosis (
de novo
amyloidosis) in DLT‐recipients. However, little is known regarding the mechanisms of the initial stage of amyloid formation in these recipients. We detected initial lesions (possible seed‐lesions) of this iatrogenic amyloidosis in two recipients following liver grafting from FAP patients. Patient 1 underwent DLT at age 65 from an FAP patient with a Val30Met TTR variant and patient 2 received DLT from an FAP patient with a Val30Leu TTR variant at age 32. Patient 2 was started on diflunisal administration from 4 years after DLT. While neither patient had symptoms of FAP, small amyloid deposits were detected on the gastroduodenal mucosae 14 months and 12 years after DLT in patient 1 and patient 2, respectively. The amyloid was analyzed using a laser microdissection system and tandem mass spectrometry. Biochemical analysis indicated that the amyloid was composed mostly of variant TTR produced from the transplanted liver in both patients. In patient 1, wild‐type TTR amyloid was detectable in the duodenal mucosa obtained 2 years after DLT. This is the first study to successfully capture the pathological and biochemical features of initial‐stage amyloid lesions in DLT recipients. The findings clearly indicate that amyloid deposition can start by deposition of variant TTR followed by deposition of wild‐type TTR, and blocking of amyloid seed formation from variant TTR may be a key to prevent or delay the development of DLT‐associated amyloidosis.
Details
- Title: Subtitle
- The pathological and biochemical identification of possible seed‐lesions of transmitted transthyretin amyloidosis after domino liver transplantation
- Creators
- Tsuneaki Yoshinaga - Shinshu University School of MedicineMasahide Yazaki - Shinshu University School of MedicineYoshiki Sekijima - Shinshu University School of MedicineFuyuki Kametani - Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical ScienceKana Miyashita - Tokyo Medical UniversityNaomi Hachiya - Tokyo Medical UniversityTomohiro Tanaka - The University of Tokyo HospitalNorihiro Kokudo - Hepato‐Biliary‐Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of TokyoKeiichi Higuchi - Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Shinshu UniversityShu‐ichi Ikeda - Shinshu University School of Medicine
- Resource Type
- Journal article
- Publication Details
- The journal of pathology. Clinical research, Vol.2(2), pp.72-79
- DOI
- 10.1002/cjp2.36
- PMID
- 27499917
- PMCID
- PMC4907057
- NLM abbreviation
- J Pathol Clin Res
- ISSN
- 2056-4538
- eISSN
- 2056-4538
- Publisher
- John Wiley and Sons Inc
- Grant note
- 25461275 ; 26670152 / Ministry of Education, Culture, Sports, Science, and Technology Ministry of Health and Welfare, Amyloid Research Committee in Japan Hokuto Foundation for Bioscience
- Alternative title
- Seeds of transmitted amyloidosis after domino liver transplantation
- Language
- English
- Date published
- 04/2016
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984094360102771
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