TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Nguyen, Thi-Huong
A1  - Medvedev, Nikolay
A1  - Delcea, Mihaela
A1  - Greinacher, Andreas
T1  - Anti-platelet factor 4/polyanion antibodies mediate a new mechanism of autoimmunity
JF  - Nature Communications
N2  - Antibodies recognizing complexes of the chemokine platelet factor 4 (PF4/CXCL4) and polyanions (P) opsonize PF4-coated bacteria hereby mediating bacterial host defense. A subset of these antibodies may activate platelets after binding to PF4/heparin complexes, causing the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). In autoimmune-HIT, anti-PF4/P-antibodies activate platelets in the absence of heparin. Here we show that antibodies with binding forces of approximately 60–100 pN activate platelets in the presence of polyanions, while a subset of antibodies from autoimmune-HIT patients with binding forces Z100 pN binds to PF4 alone in the absence of polyanions. These antibodies with high binding forces cluster PF4-molecules forming antigenic complexes which allow binding of polyanion-dependent anti-PF4/P-antibodies. The resulting immunocomplexes induce massive platelet activation in the absence of heparin. Antibody-mediated changes in endogenous proteins that trigger binding of otherwise non-pathogenic (or cofactor-dependent) antibodies may also be relevant in other antibody-mediated autoimmune disorders.
Y1  - 2017
U6  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-42190
UN  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-42190
SN  - 2041-1723
SS  - 2041-1723
VL  - 8
SP  - 14945
ER  -