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


OBJECTIVE
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.
Suvarna
S
S
Division of Hematology, Duke University Medical Center, Durham, NC 27710, USA.
Qi
R
R
Arepally
G M
GM
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D006493:Heparin / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010976:Platelet Count
D000906:Antibodies; D006493:Heparin