C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia

Rick Kapur, Katja M.J. Heitink-Pollé, Leendert Porcelijn, Arthur E.H. Bentlage, Marrie C.A. Bruin, Remco Visser, Dirk Roos, Richard B.M. Schasfoort, Masja de Haas, C. Ellen van der Schoot and Gestur Vidarsson

Key points

  • CRP enhances IgG-mediated respiratory burst and phagocytosis of platelets in vitro and their clearance in vivo.

  • CRP levels are increased in ITP patients and correlate with platelet counts and bleeding severity, and predict time to recovery.


Immune-mediated platelet destruction is most frequently caused by allo- or autoantibodies via Fcγ-receptor (FcγR)-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating other factors to play a role. Here we show that the acute-phase protein C-Reactive Protein (CRP), a ligand for Fc-receptors on phagocytes, enhances antibody-mediated platelet destruction by human phagocytes in vitro, and in vivo in mice. Without anti-platelet antibodies, CRP was found to be inert towards platelets, but it bound to phosphorylcholine exposed after oxidation triggered by anti-platelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo- and autoantibody-mediated thrombocytopenias compared to healthy controls. Within a week, IVIg-treatment in children with newly diagnosed immune thrombocytopenia led to significant decrease of CRP levels, increased platelet numbers and clinically decreased bleeding severity. Furthermore, the higher the level of CRP at diagnosis, the longer it took before stable platelet counts were reached. These data suggest CRP to amplify antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia upon infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients.

  • Submitted May 29, 2014.
  • Accepted December 15, 2014.