title: Studies on unfolded beta-microglobulin at C-terminal in dialysis-related amyloidosis.
abstract: BACKGROUND
  In 1997, Stoppini et al reported that monoclonal antibody specific to the C-terminal 92-99 of beta(2)-microglobulin (beta(2)m) had been capable of inhibiting fibrillogenesis of beta(2)m in vitro. Meanwhile, recent studies have indicated that an acidifying procedure can unfold conformation of the precursor protein, leading to fibril formation of beta(2)m as well as a transthyretin.
  
  
  METHODS
  We thus prepared monoclonal antibody specific to the C-terminal 92-99 (mAb 92-99), and investigated its reactivity in plasma ultrafiltrate and amyloid tissues from 18 hemodialysis patients with dialysis-related amyloidosis (DRA).
  
  
  RESULTS
  beta(2)m extracted from ultrafiltrate showed no reaction for mAb 92-99, whereas acidified beta(2)m from ultrafiltrate showed a reaction for mAb 92-99. Similarly, a homogenate of carpal amyloid tissues showed a strong reaction for mAb 92-99 on immunoblotting. Immunohistochemical study showed also a distinct staining for mAb 92-99 in 7 Congophilic specimens from DRA patients. More interestingly, staining for mAb 92-99 could be found in most, though not all, non-Congophilic tissues.
  
  
  CONCLUSIONS
  This study demonstrates that the monoclonal antibody specific to the C-terminal 92-99 of beta(2)m can detect the conformational intermediate in amyloidogenesis of beta(2)m ex vivo, and demonstrates that an unfolded beta(2)m at C-terminal could be found not only in Congophilic area but even in non-Congophilic area as well.
authors.affiliation: Suiyukai Clinic, Nara, Japan. motomiya@silver.ocn.ne.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Motomiya
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Katsuki
authors.initials: K
authors.lastname: Haraoka
authors.forename: Xuguo
authors.initials: X
authors.lastname: Sun
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Izumi
authors.initials: I
authors.lastname: Amano
authors.forename: Tomonori
authors.initials: T
authors.lastname: Uchimura
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D002349:Carpal Tunnel Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011489:Protein Denaturation; D017510:Protein Folding; D006435:Renal Dialysis / Q000009:adverse effects*; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D001613:beta 2-Microglobulin