Fine mapping of inhibitory anti-factor V antibodies using factor V C2 domain mutants: Identification of two antigenic epitopes involved in phospholipid binding

T. Izumi, Suhng Wook Kim, A. Greist, S. Macedo-Ribeiro, P. Fuentes-Prior, W. Bode, W. H. Kane, T. L. Ortel

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Hemorrhagic factor V inhibitors frequently bind to the second C-type (C2) domain of factor V and interfere with phospholipid binding. To define specific residues recognized by inhibitors from four patients (one bovine thrombin-induced and three spontaneous antibodies), epitope mapping was performed using recombinant human factor V lacking most of the B-type domain (FV des B) and alanine-substituted mutants within the C2 domain (FV des B C2 mutants). FV des B C2 mutants located in the region between Lys2060 and Glu2069 were resistant to inhibition by three IgG preparations including the bovine thrombin-induced antibody in both prothrombinase and phospholipid-binding assays. In contrast, mutations at Lys2087 and Lys2092/Glu2096 were significantly resistant to inhibition by the fourth IgG preparation in both prothrombinase and phospholipid-binding assays. These results confirm interference of phospholipid binding by hemorrhagic factor V inhibitors and support the role(s) of these residues in phospholipid binding.

Original languageEnglish
Pages (from-to)1048-1054
Number of pages7
JournalThrombosis and Haemostasis
Volume85
Issue number6
Publication statusPublished - 2001 Jul 5
Externally publishedYes

Keywords

  • C2 domain
  • Epitope mapping
  • Factor V
  • Hemorrhagic inhibitor
  • Phospholipid binding

ASJC Scopus subject areas

  • Hematology

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