Progression of transthyretin amyloid neuropathy after liver transplantation.
OBJECTIVE
To biochemically characterize peripheral nerve amyloid in subjects with transthyretin (TTR) amyloidosis and assess effect of orthotopic liver transplantation (OLT) on progression of neuropathy.


METHODS
Amyloid fibrils were isolated from peripheral nerve tissues of 6 patients with TTR amyloidosis who were heterozygous for an amyloid-associated TTR mutation. Ratio of variant to wild-type TTR in the fibrils was determined by amino acid sequencing of tryptic peptides containing either the variant amino acid residue or the corresponding normal amino acid.


RESULTS
Amyloid fibrils from 3 subjects who died without having received a liver transplant were composed of 60%-65% variant TTR and 35%-40% wild-type. Amyloid fibrils from a subject who died 5 years after liver transplantation contained 25% variant and 75% wild-type TTR.


CONCLUSIONS
Ratios of variant to wild-type TTR in amyloid patients heterozygous for an amyloid-associated TTR mutation are similar to published ratios for amyloid fibrils in cardiac tissue. Survival after liver transplantation for TTR amyloidosis may be associated with progression of neuropathy due to continued deposition of amyloid derived from wild-type TTR.
Liepnieks
Juris J
JJ
Indiana University School of Medicine, Department of Pathology and Laboratory Medicine, 635 Barnhill Drive, Indianapolis, IN 46202-5126, USA. mdbenson@iupui.edu
Zhang
Lucy Q
LQ
Benson
Merrill D
MD
D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism; D017772:Amyloid Neuropathies / Q000235:genetics / Q000401:mortality / Q000601:surgery; D004252:DNA Mutational Analysis; D018450:Disease Progression; D006579:Heterozygote; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000601:surgery; D016031:Liver Transplantation / Q000401:mortality*; D008875:Middle Aged; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism*
D000682:Amyloid; D011228:Prealbumin