Steady turnover of amyloid fibril proteins in gastric mucosa after liver transplantation in familial amyloid polyneuropathy

Abstract

Introduction: Our previous study demonstrated marked regression of amyloid deposits in abdominal fat tissues of familial amyloid polyneuropathy (FAP) patients treated with liver transplantation (LT). To determine whether similar changes in deposited amyloid can also occur in other organs, we examined gastric mucosal amyloid before and after LT in FAP patients with ATTRV30M.

Methods: We histopathologically and biochemically investigated gastric mucosal amyloid before and after LT in six FAP patients with ATTRV30M.The amounts of amyloid deposits in biopsied gastric mucosa were determined by microscopy, and the proportion of wild-type transthyretin (TTR) in extracted amyloid fibril proteins was assayed by liquid chromatography-ion trap mass spectrometry. Similar examinations were also performed in 21 untreated FAP patients and 13 transplanted patients with ATTRV30M.

Results: The amount of deposited amyloid was not markedly different before and after LT in six patients. However, the composition ratios of wild-type TTR in gastric mucosal amyloid increased markedly from 20.0% ± 11.4% before LT to 43.2% ± 13.8% after LT. In addition, the ratio of wild-type TTR in all transplanted patients was significantly higher than that in untransplanted patients (72.7% ± 25.5%, 23.8% ± 14.3%, respectively).

Conclusions: Our results showed that the components of amyloid fibril proteins in gastric mucosa of transplanted FAP patients are different from those in untreated patients: a significant portion of preexisting ATTRV30M-derived amyloid seemed to be replaced by wild-type TTR-derived amyloid postoperatively, indicating that continuous turnover of amyloid deposits can occur in all organs in transplanted FAP patients. It was also confirmed that wild-type TTR plays an important role in the pathogenesis of postoperative amyloid deposition in transplanted FAP patients.

• Amyloid
• amyloid turnover
• liver transplantation
• regression of amyloid
• transthyretin
• variant
• wild-type