Optimization of a murine immunization model for study of PF4/heparin antibodies.

Journal Article (Journal Article)

SUMMARY BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a life-threatening thrombotic illness caused by drug-dependent antibodies recognizing complexes of platelet factor 4 (PF4) and heparin. Little is known about the immune pathogenesis of HIT, in particular factors influencing PF4/heparin antibody formation. To gain insight into the biologic basis of heparin sensitization, we have recently developed an animal model using wild-type (WT) mice in which murine PF4/heparin antibodies (anti-mPF4/H) arise de novo after antigen challenge. OBJECTIVES AND METHODS: This report describes technical refinements to the murine model and describes additional biologic features of the immune response to mPF4/heparin. RESULTS: Our studies indicate that antibody responses to mPF4/heparin are dependent on murine strain, injection routes and doses of mPF4 and heparin. C57BL/6 mice are more immunologically responsive to mPF4/heparin antigen than BALB/c mice and robust immunization can be achieved with intravenous, but not intraperitoneal, administration of antigen. We also observe a direct relationship between initial concentrations of mPF4 and antibody levels. Additionally, we demonstrate that mPF4/H immune response in mice decays with time, is not associated with thrombocytopenia and displays characteristics of immune recall on re-exposure to antigen. CONCLUSIONS: These studies describe and characterize a murine model for studying the immunologic basis of PF4/heparin sensitization.

Full Text

Duke Authors

Cited Authors

  • Suvarna, S; Qi, R; Arepally, GM

Published Date

  • May 2009

Published In

Volume / Issue

  • 7 / 5

Start / End Page

  • 857 - 864

PubMed ID

  • 19245419

Pubmed Central ID

  • PMC3711941

Electronic International Standard Serial Number (EISSN)

  • 1538-7836

Digital Object Identifier (DOI)

  • 10.1111/j.1538-7836.2009.03330.x


  • eng

Conference Location

  • England