title: Increased C1q, C4 and C3 deposition on platelets in patients with systemic lupus erythematosus--a possible link to venous thrombosis?
abstract: OBJECTIVE
  Patients with systemic lupus erythematosus (SLE) have an increased risk of developing vascular diseases (VD) such as myocardial infarction, stroke and venous thrombosis, which can only partly be explained by traditional risk factors. The role of platelets in this process has not been extensively studied. Platelet activation supports complement binding to the platelet surface, and increased C4d has been seen on platelets in SLE patients as well as in non-rheumatic patients with stroke. In this study we investigated in vivo platelet deposition of the classical complement pathway components C1q, C4d and C3d in relation to VD in SLE patients. Furthermore, the ability of serum to support in vitro complement deposition on fixed heterologous platelets was analyzed.
  
  
  METHODS
  Blood from 69 SLE patients and age- and sex-matched healthy individuals was collected in sodium-citrate tubes and platelets isolated by centrifugation. Complement deposition on platelets was detected by flow cytometry.
  
  
  RESULTS
  We could demonstrate that SLE patients had increased C1q, C3d and C4d deposition on platelets as compared to healthy controls (p < 0.0001). SLE patients with a history of venous thrombosis had increased complement deposition on platelets as compared to SLE patients without this manifestation (p < 0.05). In vitro studies demonstrated that serum from patients with lupus anticoagulant, venous thrombosis or antiphospholipid antibody syndrome supported increased platelet C4d deposition in vitro as compared to SLE patients without these manifestations (p < 0.05). Our data support the hypothesis that platelet activation and the subsequent complement deposition on platelets are central in the development of venous thrombosis in SLE.
  
  
  CONCLUSIONS
  Altogether we suggest that complement deposition on platelets could reflect important pathogenetic events related to the development of venous thrombosis in SLE and might be used as a marker for venous thrombosis in SLE.
authors.affiliation: Department of Clinical Sciences, Section of Rheumatology, Lund University and Skåne University Hospital, Sweden. christian.lood@med.lu.se
authors.forename: C
authors.initials: C
authors.lastname: Lood
authors.forename: S
authors.initials: S
authors.lastname: Eriksson
authors.forename: B
authors.initials: B
authors.lastname: Gullstrand
authors.forename: A
authors.initials: A
authors.lastname: Jönsen
authors.forename: G
authors.initials: G
authors.lastname: Sturfelt
authors.forename: L
authors.initials: L
authors.lastname: Truedsson
authors.forename: A A
authors.initials: AA
authors.lastname: Bengtsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000276:immunology*; D016022:Case-Control Studies; D015922:Complement C1q / Q000032:analysis*; D015933:Complement C3d / Q000032:analysis*; D015935:Complement C4b / Q000032:analysis*; D003171:Complement Pathway, Classical; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D015539:Platelet Activation; D012307:Risk Factors; D015854:Up-Regulation; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology* / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016682:Lupus Coagulation Inhibitor; D010446:Peptide Fragments; D015922:Complement C1q; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d