title: A novel localized amyloidosis associated with lactoferrin in the cornea.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, Kumamoto University School of Medicine, Kumamoto, Japan. yukio@kaiju.medic.kumamoto-u.ac.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kai
authors.forename: Shoichi
authors.initials: S
authors.lastname: Katsuragi
authors.forename: Hisayasu
authors.initials: H
authors.lastname: Terazaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nozawa
authors.forename: Toshiya
authors.initials: T
authors.lastname: Okuda
authors.forename: Shogo
authors.initials: S
authors.lastname: Misumi
authors.forename: Noriko
authors.initials: N
authors.lastname: Matsunaga
authors.forename: Kanako
authors.initials: K
authors.lastname: Hata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tajiri
authors.forename: Shozo
authors.initials: S
authors.lastname: Shoji
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Katsuki
authors.initials: K
authors.lastname: Haraoka
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.forename: Koki
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ando
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchino
mesh_terms: 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
chemical_list: D000682:Amyloid; D007781:Lactoferrin