title: Von Willebrand Factor Interacts with Surface-Bound C1q and Induces Platelet Rolling.
abstract: Premature atherosclerosis and thrombotic complications are major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, the high incidence of these complications cannot be explained by traditional risk factors alone, suggesting direct effects of an activated immune system on hemostasis. The unexpected nucleotide sequence homology between SLE patient-derived autoantibodies against complement C1q (Fab anti-C1q) and von Willebrand factor (VWF) led us to investigate a potential interaction between the complement and hemostatic systems on the level of initiating molecules. VWF was found to bind to surface-bound C1q under static conditions. The binding could specifically be inhibited by Fab anti-C1q and C1q-derived peptides. Under shear stress the C1q-VWF interaction was enhanced, resembling the binding of VWF to collagen I. Additionally, we could show that C1q-VWF complexes induced platelet rolling and firm adhesion. Furthermore, we observed VWF binding to C1q-positive apoptotic microparticles and cholesterol crystals, as well as increased VWF deposition in C1q-positive glomeruli of SLE patients compared with control nephropathy. We show, to our knowledge for the first time, binding of VWF to C1q and thus a direct interaction between starter molecules of hemostasis and the classical pathway of complement. This direct interaction might contribute to the pathogenic mechanisms in complement-mediated, inflammatory diseases.
authors.affiliation: Department of Biomedicine, University Hospital, 4031 Basel, Switzerland; robert.koelm@unibas.ch.
authors.forename: Robert
authors.initials: R
authors.lastname: Kölm
authors.affiliation: University Clinic of Hematology and Central Hematology Laboratory, Bern University Hospital, 3010 Bern, Switzerland.|Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
authors.forename: Monica
authors.initials: M
authors.lastname: Schaller
authors.affiliation: INSERM UMR S-1138, Cordeliers Research Center, Complement and Diseases Team, 75006 Paris, France.
authors.forename: Lubka T
authors.identifier: 0000-0002-9940-0324
authors.initials: LT
authors.lastname: Roumenina
authors.affiliation: Department of Biomedicine, University Hospital, 4031 Basel, Switzerland.
authors.forename: Iga
authors.identifier: 0000-0002-6134-5083
authors.initials: I
authors.lastname: Niemiec
authors.affiliation: University Clinic of Hematology and Central Hematology Laboratory, Bern University Hospital, 3010 Bern, Switzerland.|Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
authors.forename: Johanna A
authors.identifier: 0000-0002-1300-7135
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.affiliation: Department of Biomedicine, University Hospital, 4031 Basel, Switzerland.
authors.forename: Elham
authors.initials: E
authors.lastname: Khanicheh
authors.affiliation: Department of Biomedicine, University Hospital, 4031 Basel, Switzerland.|Division of Cardiology, University Hospital, 4031 Basel, Switzerland.
authors.forename: Beat A
authors.identifier: 0000-0001-6295-3630
authors.initials: BA
authors.lastname: Kaufmann
authors.affiliation: Institute of Pathology, University Hospital, 4031 Basel, Switzerland; and.
authors.forename: Helmut
authors.identifier: 0000-0003-1755-2170
authors.initials: H
authors.lastname: Hopfer
authors.affiliation: Department of Biomedicine, University Hospital, 4031 Basel, Switzerland.|Division of Internal Medicine, University Hospital, 4031 Basel, Switzerland.
authors.forename: Marten
authors.initials: M
authors.lastname: Trendelenburg
mesh_terms: D000936:Antigen-Antibody Complex / Q000378:metabolism; D017209:Apoptosis; D050197:Atherosclerosis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D015922:Complement C1q / Q000378:metabolism*; D006487:Hemostasis; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000276:immunology; D015539:Platelet Activation; D011485:Protein Binding; D013927:Thrombosis / Q000276:immunology*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D024042:Collagen Type I; D014841:von Willebrand Factor; D015922:Complement C1q