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

22 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

Fingerprint

Factor V
Epitopes
Phospholipids
Antibodies
Thromboplastin
Thrombin
Immunoglobulin G
Epitope Mapping
Alanine
C2 Domains
Mutation

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Fine mapping of inhibitory anti-factor V antibodies using factor V C2 domain mutants : Identification of two antigenic epitopes involved in phospholipid binding. / Izumi, T.; Kim, Suhng Wook; Greist, A.; Macedo-Ribeiro, S.; Fuentes-Prior, P.; Bode, W.; Kane, W. H.; Ortel, T. L.

In: Thrombosis and Haemostasis, Vol. 85, No. 6, 05.07.2001, p. 1048-1054.

Research output: Contribution to journalArticle

Izumi, T, Kim, SW, Greist, A, Macedo-Ribeiro, S, Fuentes-Prior, P, Bode, W, Kane, WH & Ortel, TL 2001, 'Fine mapping of inhibitory anti-factor V antibodies using factor V C2 domain mutants: Identification of two antigenic epitopes involved in phospholipid binding', Thrombosis and Haemostasis, vol. 85, no. 6, pp. 1048-1054.
Izumi, T. ; Kim, Suhng Wook ; Greist, A. ; Macedo-Ribeiro, S. ; Fuentes-Prior, P. ; Bode, W. ; Kane, W. H. ; Ortel, T. L. / Fine mapping of inhibitory anti-factor V antibodies using factor V C2 domain mutants : Identification of two antigenic epitopes involved in phospholipid binding. In: Thrombosis and Haemostasis. 2001 ; Vol. 85, No. 6. pp. 1048-1054.
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