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

R. Kapur, K.M.J. Heitink-Pollé, L. Porcelijn, A.E.H. Bentlange, M.C.A. Bruin, R. Visser, D. Roos, Richardus B.M. Schasfoort, G. Vidarsson, M. de Haas, C. E. van der Schoot

Research output: Contribution to journalArticleAcademicpeer-review

43 Citations (Scopus)

Abstract

Immune-mediated platelet destruction is most frequently caused by allo- or autoantibodies via Fcγ receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors 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 antiplatelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo- and autoantibody-mediated thrombocytopenias compared with healthy controls. Within a week, intravenous immunoglobulin 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 that CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients.
Original languageEnglish
Pages (from-to)1793-1802
JournalBlood
Volume125
Issue number11
DOIs
Publication statusPublished - 2015

Keywords

  • IR-98630
  • METIS-313486

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