Article
Lab Invest 2002, 82:757–766
A Novel Localized Amyloidosis Associated with Lactoferrin in the Cornea
Yukio Ando1, Masaaki Nakamura2, Hirofumi Kai5, Shoichi Katsuragi7, Hisayasu Terazaki3, Takayuki Nozawa8, Toshiya Okuda4, Shogo Misumi6, Noriko Matsunaga1, Kanako Hata1,3, Takahiro Tajiri1, Shozo Shoji6, Taro Yamashita2, Katsuki Haraoka1,3, Konen Obayashi2, Koki Matsumoto4, Masayuki Ando3 and Makoto Uchino2
- 1Department of Laboratory Medicine, Kumamoto University School of Medicine, Oe-honmachi, Kumamoto, Japan
- 2Department of Neurology, Kumamoto University School of Medicine, Oe-honmachi, Kumamoto, Japan
- 3First Department of Internal Medicine, Kumamoto University School of Medicine, Oe-honmachi, Kumamoto, Japan
- 4Department of Ophthalmology, Kumamoto University School of Medicine, Oe-honmachi, Kumamoto, Japan
- 5Department of Pharmacological Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Kumamoto, Japan
- 6Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Kumamoto, Japan
- 7Department of Psychiatry, Kikuchi Ryoyo-sho Hospital, Oaza-Fukuhara, Koshi-machi, Kikuchi-gun, Japan
- 8Department of Pathology, Kanazawa Medical University Hospital, Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa, Japan
Correspondence: Dr. Yukio Ando, Department of Laboratory Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-0811, Japan. E-mail: yukio@kaiju.medic.kumamoto-u.ac.jp
Received 29 January 2002.
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.
