title: C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia.
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.
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Rick
authors.initials: R
authors.lastname: Kapur
authors.affiliation: Department of Pediatric Hematology-Oncology, University Medical Center Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands;
authors.forename: Katja M J
authors.initials: KM
authors.lastname: Heitink-Pollé
authors.affiliation: Department of Thrombocyte and Leukocyte Serology, Sanquin Diagnostic Services, Amsterdam, The Netherlands;
authors.forename: Leendert
authors.initials: L
authors.lastname: Porcelijn
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Arthur E H
authors.initials: AE
authors.lastname: Bentlage
authors.affiliation: Department of Pediatric Hematology-Oncology, University Medical Center Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands;
authors.forename: Marrie C A
authors.initials: MC
authors.lastname: Bruin
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Remco
authors.initials: R
authors.lastname: Visser
authors.affiliation: Department of Blood Cell Research, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Dirk
authors.initials: D
authors.lastname: Roos
authors.affiliation: Medical Cell Biophysics, MIRA Institute, University of Twente, Enschede, The Netherlands.
authors.forename: Richard B M
authors.initials: RB
authors.lastname: Schasfoort
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Masja
authors.initials: M
authors.lastname: de Haas
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: C Ellen
authors.initials: CE
authors.lastname: van der Schoot
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Gestur
authors.initials: G
authors.lastname: Vidarsson
mesh_terms: D000210:Acute-Phase Reaction / Q000097:blood / Q000276:immunology; D000818:Animals; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002097:C-Reactive Protein / Q000276:immunology*; D002648:Child; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism*; D010587:Phagocytosis; D015539:Platelet Activation; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000276:immunology* / Q000628:therapy; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D008024:Ligands; D017452:Receptors, IgG; D002097:C-Reactive Protein