Deposition and passage of transthyretin through the blood-nerve barrier in recipients of familial amyloid polyneuropathy livers

• Published in: Laboratory investigation Vol. 84; no. 7; pp. 865 - 873
• Main Authors: Sousa, Mónica M, Ferrão, José, Fernandes, Rui, Guimarães, António, B Geraldes, José, Perdigoto, Rui, Tomé, Luís, Mota, Oscar, Negrão, Luís, Furtado, Alexandre Linhares, Saraiva, Maria João
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2004; Nature Publishing; Nature Publishing Group
• Subjects: Adult; Amyloid Neuropathies, Familial - metabolism; Amyloid Neuropathies, Familial - pathology; Amyloid Neuropathies, Familial - surgery; Amyloidosis - etiology; Biological and medical sciences; Biopsy; Biotechnology; blood-nerve barrier; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; domino liver transplantation; familial amyloid polyneuropathy; Female; Fundamental and applied biological sciences. Psychology; Humans; Liver - innervation; Liver - metabolism; Liver Transplantation; Male; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neurology; peripheral nerve; Prealbumin - metabolism; Skin - pathology; transthyretin; blood-nerve barrier; familial amyloid polyneuropathy; peripheral nerve; transthyretin; domino liver transplantation; Human; Biotechnology; Nervous system diseases; Liver; Barrier; Recipient; Polyneuropathy; Blood; Thyroxine binding prealbumin; Clinical biology; Amyloid; Peripheral nerve disease; Deposition
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.3700107

Familial amyloid polyneuropathy (FAP) is characterized by deposition of mutated transthyretin (TTR) in the peripheral nervous system. Prior to amyloid fibrils, nonfibrillar TTR aggregates are deposited inducing oxidative stress with increased nitration (3-NT). As the major source of TTR is the liver, liver transplantation (LT) is used to halt FAP. Given the shortage of liver donors, domino LT (DLT) using FAP livers is performed. The correlation between TTR deposition in the skin and nerve was tested in biopsies from normal individuals, asymptomatic carriers (FAP 0) and FAP patients; in FAP 0, nonfibrillar TTR was observed both in the skin and nerve in the same individuals; in patients, amyloid was detected in both tissues. The occurrence of amyloidosis in recipients of FAP livers was evaluated 1–7 years after DLT: TTR deposition occurred in the skin 3 years after transplantation either as amyloid or aggregates; in one of the recipients, fibrillar TTR was present in the epineurium 6 years after DLT. Deposits were scarce and 3-NT immunostaining was irrelevant. Nerve biopsies from DLT recipients had no FAP-related neuropathy. Our findings suggest that TTR amyloid formation occurs faster than predicted and that TTR of liver origin can cross the blood-nerve barrier. Recipients of FAP livers should be under surveillance for TTR deposition and tissue damage.