title: Impact of antibodies against amyloidogenic transthyretin (ATTR) on phenotypes of patients with familial amyloidotic polyneuropathy (FAP) ATTR Valine30Methionine.
abstract: BACKGROUND
  This study investigated whether a relationship exists between the presence of de novo antibodies and the clinical manifestations of familial amyloidotic polyneuropathy (FAP).
  
  
  METHODS
  Serum samples were collected from 25 Japanese and 6 Swedish FAP amyloidogenic transthyretin (ATTR) Valine30Methionine (V30M) patients, 4 asymptomatic Japanese ATTR V30M gene carriers, and 24 Japanese healthy volunteers. Study methods included enzyme-linked immunosorbent assay (ELISA) and mass spectrometry.
  
  
  RESULTS
  Three Japanese and 5 Swedish patients had significantly higher levels of antibodies against ATTR than did healthy volunteers and asymptomatic gene carriers (P<0.05). All 8 patients with higher antibody levels were late-onset cases. The ratio of wild-type TTR to ATTR V30M in serum from the high-antibody group was higher than that of the low-antibody group. ELISA results revealed two epitopes at positions 24-35 and 105-115 of ATTR V30M. We found a significant positive correlation between levels of the antibody at positions 24-35 and the age at FAP onset (r=0.751, P<0.05). An age-dependent increase in the occurrence of antibodies was observed in these patients with an epitope at positions 24-35.
  
  
  CONCLUSIONS
  These findings may help explain the differences in early- and late-onset FAP and/or the progression of FAP.
authors: Diagnostic Unit for Amyloidosis, Department of Laboratory Medicine, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto, Japan. konen@fc.kuh.kumamoto-u.ac.jp
authors: Konen
authors: K
authors: Obayashi
authors: Masayoshi
authors: M
authors: Tasaki
authors: Hirofumi
authors: H
authors: Jono
authors: Mitsuharu
authors: M
authors: Ueda
authors: Satoru
authors: S
authors: Shinriki
authors: Yohei
authors: Y
authors: Misumi
authors: Taro
authors: T
authors: Yamashita
authors: Toshinori
authors: T
authors: Oshima
authors: Teruya
authors: T
authors: Nakamura
authors: Shinji
authors: S
authors: Ikemizu
authors: Intissar
authors: I
authors: Anan
authors: Ole
authors: O
authors: Suhr
authors: Yukio
authors: Y
authors: Ando
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D028227:Amyloid Neuropathies, Familial / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D013058:Mass Spectrometry; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics / Q000276:immunology*; D013548:Sweden
chemical_list: D000682:Amyloid; D000906:Antibodies; D011228:Prealbumin; C041120:amyloid prealbumin