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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Izumi, T; Kim, SW; Greist, A; Macedo-Ribeiro, S; Fuentes-Prior, P; Bode, W; Kane, WH; Ortel, TL

Published Date

  • June 2001

Published In

Volume / Issue

  • 85 / 6

Start / End Page

  • 1048 - 1054

PubMed ID

  • 11434683

International Standard Serial Number (ISSN)

  • 0340-6245

Language

  • eng

Conference Location

  • Germany