@article{NguyenMedvedevDelceaetal.2017,
  author    = {Thi-Huong Nguyen and Nikolay Medvedev and Mihaela Delcea and Andreas Greinacher},
  title     = {Anti-platelet factor 4/polyanion antibodies mediate a new mechanism of autoimmunity},
  series   = {Nature Communications},
  volume    = {8},
  issn      = {2041-1723},
  url       = {https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-42190},
  pages     = {14945},
  year      = {2017},
  abstract  = {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.},
  language  = {en}
}