Discovery of an uncovered region in fibrin clots and its clinical significance

Sci Rep. 2013:3:2604. doi: 10.1038/srep02604.

Abstract

Despite the pathological importance of fibrin clot formation, little is known about the structure of these clots because X-ray and nuclear magnetic resonance (NMR) analyses are not applicable to insoluble proteins. In contrast to previously reported anti-fibrin monoclonal antibodies (mAbs), our anti-fibrin clot mAb (clone 102-10) recognises an uncovered region that is exposed only when a fibrin clot forms. The epitope of the 102-10 mAb was mapped to a hydrophobic region on the Bβ chain that interacted closely with a counterpart region on the γ chain in a soluble state. New anti-Bβ and anti-γ mAbs specific to peptides lining the discovered region appeared to bind exclusively to fibrin clots. Furthermore, the radiolabelled 102-10 mAb selectively accumulated in mouse spontaneous tumours, and immunohistochemistry using this mAb revealed greater fibrin deposition in World Health Organization (WHO) grade 4 glioma than in lower-grade gliomas. Because erosive tumours are apt to cause micro-haemorrhages, even early asymptomatic tumours detected with a radiolabelled 102-10 mAb may be aggressively malignant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Antibody Complex / chemistry*
  • Antigen-Antibody Complex / immunology*
  • Binding Sites
  • Blood Coagulation / immunology*
  • Epitope Mapping / methods*
  • Fibrin / chemistry*
  • Fibrin / immunology*
  • Mice
  • Protein Binding
  • Protein Structure, Tertiary

Substances

  • Antigen-Antibody Complex
  • Fibrin