PF4/heparin complexes are T cell–dependent antigens

Heparin-induced thrombocytopenia (HI66670) is a life-threatening, thrombotic disorder associated with development of anti–platelet factor 4 (anti-PF4)/heparin autoantibodies. Little is known about the antigenic and cellular requirements that initiate the immune response to these complexes. To begin...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2005-08, Vol.106 (3), p.929-931
Main Authors: Suvarna, Shayela, Rauova, Lubica, McCracken, Emily K.E., Goss, Christina M., Sachais, Bruce S., McKenzie, Steven E., Reilly, Michael P., Gunn, Michael Dee, Cines, Douglas B., Poncz, Mortimer, Arepally, Gowthami
Format: Article
Language:English
Subjects:
Animals
Antibody Formation
Autoantibodies - biosynthesis
Biological and medical sciences
Drug toxicity and drugs side effects treatment
Hematologic and hematopoietic diseases
Hemostasis, Thrombosis, and Vascular Biology
Heparin - administration & dosage
Heparin - immunology
Immunization
Medical sciences
Mice
Mice, Inbred BALB C
Miscellaneous (drug allergy, mutagens, teratogens...)
Pharmacology. Drug treatments
Platelet diseases and coagulopathies
Platelet Factor 4 - administration & dosage
Platelet Factor 4 - immunology
T-Lymphocytes - immunology
Thrombocytopenia - chemically induced
Thrombocytopenia - immunology
Thymus Gland - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Heparin-induced thrombocytopenia (HI66670) is a life-threatening, thrombotic disorder associated with development of anti–platelet factor 4 (anti-PF4)/heparin autoantibodies. Little is known about the antigenic and cellular requirements that initiate the immune response to these complexes. To begin to delineate mechanisms of autoantibody formation in HIT, we studied the immunizing effects of murine PF4 (mPF4)/heparin in mice with and without thymic function. Euthymic mice were injected with mPF4/heparin complexes, mPF4, heparin, or buffer. Mice injected with mPF4/heparin, but not mPF4 or heparin alone, developed heparin-dependent autoantibodies that shared serologic and functional characteristics of human HIT antibodies, including preferential binding to mPF4/heparin complexes and causing heparin- and FcRγIIA-dependent platelet activation. In contrast, athymic mice did not develop HIT-like antibodies. Taken together, these studies establish that PF4/heparin complexes are highly immunogenic and elicit self-reacting anti-PF4/heparin antibodies in a T cell–dependent manner.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-12-4955