Degree of polymer organization decreases the binding of a monoclonal antibody raised against the beta-chain amino terminus of fibrin.
Accurate non-invasive diagnosis of deep venous thrombosis and pulmonary embolism remains an elusive goal. Radiolabeled antibodies specific for the epitope exposed on the beta-chain of fibrin after fibrino-peptide B release (anti-beta) enabled in situ imaging of thrombi in experimental subjects with nuclear medicine techniques. When used in patients anticoagulated for thrombo-embolic disease, however, the antibody was unable to reliably image the thrombi. We postulated that the neoepitope on the beta-chain of fibrin is covered up as fibrin organizes into a polymer network and is therefore exposed to the antibody only during active incorporation of fibrin subunits. We determined the equilibrium binding kinetics of an anti-beta monoclonal antibody to fibrin in various stages of organization. The concentration of exposed epitopes on immobilized fibrin monomers was equal to the molar concentration of fibrin beta-chains. The percentage of beta-chains exposed to the antibodies markedly decreased as the fibrin network was allowed to organize, a process catalyzed by calcium.


CONCLUSIONS
The beta-chain amino terminus of fibrin is exposed transiently as subunits are added to the enlarging fibrin network. Anti-beta antibodies bind preferentially to actively enlarging fibrin polymers.
Morris
T A
TA
University of California, School of Medicine, UCSD Medical Center, San Diego.
Marsh
J J
JJ
Fagnani
R
R
Hagan
M
M
Moser
K M
KM
D000911:Antibodies, Monoclonal; D000937:Antigen-Antibody Reactions; D001704:Biopolymers; D005337:Fibrin / Q000276:immunology*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology*; D011655:Pulmonary Embolism / Q000097:blood / Q000175:diagnosis*; D013924:Thrombophlebitis / Q000097:blood / Q000175:diagnosis*
D000911:Antibodies, Monoclonal; D001704:Biopolymers; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D005337:Fibrin; D006493:Heparin