A monoclonal Antibody that Inhibits fibrin Polymerization and Cross-Linking of the Fibrin γ-Chains

Abstract

IEF-13 is an anti-human fibrinogen monoclonal antibody that belongs to the subclass of IgGi with κ-type light chains. IEF-13 recognizes the carboxy-terminal segment of the fibrinogen γ-chain containing the factor XIIIa-catalyzed cross-linking sites, but it is unable to react with the preformed γ-dimer, indicating that the local conformation of the carboxyterminal γ-chain segment contributes to the integrity of epitope for this antibody. As anticipated, IEF-13 inhibited factor XIIIa-catalyzed crosslinking of the fibrin γ-chains. Of interest was a finding that the antibody inhibited fibrin monomer polymerization at a molar ratio to fibrin monomer ≥1 even in the absence of factor XIIIa and Ca2+. Thus it appears that the antiparallel alignment of two γ-chains from different molecules is closely linked with the interaction of fibrin monomers in the formation of double-stranded fibrin protofibrils. In an in vivo situation, crosslinking of the γ-chains readily progresses when factor XIIIa and Ca2+ are present in fibrin clots.