A novel localized amyloidosis associated with lactoferrin in the cornea.
We report a novel localized amyloidosis associated with lactoferrin. To elucidate the precursor protein of corneal amyloidosis associated with trichiasis, we analyzed amyloid deposits from three patients by histopathology and biochemistry. Amyloid deposits showed immunoreactivity, confirmed by electron microscopy, for only anti-human lactoferrin antibody. Electrophoresis of amyloid fibrils revealed lactoferrin with and without sugar chains; N-terminal sequence analysis revealed full-length lactoferrin and a truncated tripeptide of N-terminal amino acids, Gly-Arg-Arg. Carboxymethylated wild-type lactoferrin formed amyloid fibrils in vitro. Lactoferrin gene analysis in the three patients revealed a Glu561Asp mutation in all of the patients and a compound heterozygote of Ala11Thr and Glu561Asp mutations in one patient. A heterozygotic Glu561Asp mutation appeared in 44.8% of healthy Japanese volunteers, suggesting that the mutation may not be an essential mutation for amyloid formation (p = 0.104). Results thus suggest that lactoferrin is this precursor protein.
Ando
Yukio
Y
Department of Laboratory Medicine, Kumamoto University School of Medicine, Kumamoto, Japan. yukio@kaiju.medic.kumamoto-u.ac.jp
Nakamura
Masaaki
M
Kai
Hirofumi
H
Katsuragi
Shoichi
S
Terazaki
Hisayasu
H
Nozawa
Takayuki
T
Okuda
Toshiya
T
Misumi
Shogo
S
Matsunaga
Noriko
N
Hata
Kanako
K
Tajiri
Takahiro
T
Shoji
Shozo
S
Yamashita
Taro
T
Haraoka
Katsuki
K
Obayashi
Konen
K
Matsumoto
Koki
K
Ando
Masayuki
M
Uchino
Makoto
M
D000328:Adult; D000368:Aged; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D003316:Corneal Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D005140:Eyelashes / Q000473:pathology; D005141:Eyelid Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D007781:Lactoferrin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation
D000682:Amyloid; D007781:Lactoferrin