title: Platelet activation and anti-phospholipid antibodies collaborate in the activation of the complement system on platelets in systemic lupus erythematosus.
abstract: Anti-phospholipid (aPL) antibodies are important contributors to development of thrombosis in patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE). The underlying mechanism of aPL antibody-mediated thrombosis is not fully understood but existing data suggest that platelets and the complement system are key components. Complement activation on platelets is seen in SLE patients, especially in patients with aPL antibodies, and has been related to venous thrombosis and stroke. The aim of this study was to investigate if aPL antibodies could support classical pathway activation on platelets in vitro as well as in SLE patients. Furthermore, we investigated if complement deposition on platelets was associated with vascular events, either arterial or venous, when the data had been adjusted for traditional cardiovascular risk factors. Finally, we analyzed if platelet complement deposition, both C1q and C4d, was specific for SLE. We found that aPL antibodies supported C4d deposition on platelets in vitro as well as in SLE patients (p = 0.001 and p<0.05, respectively). Complement deposition on platelets was increased in SLE patients when compared with healthy individuals (p<0.0001). However, high levels of C4d deposition and a pronounced C1q deposition were also seen in patients with rheumatoid arthritis and systemic sclerosis. In SLE, C4d deposition on platelets was associated with platelet activation, complement consumption, disease activity and venous (OR = 5.3, p = 0.02), but not arterial, thrombosis, observations which were independent of traditional cardiovascular risk factors. In conclusion, several mechanisms operate in SLE to amplify platelet complement deposition, of which aPL antibodies and platelet activation were identified as important contributors in this investigation. Complement deposition on platelets was identified as a marker of venous, but not arterial thrombosis, in SLE patients independently of traditional risk factors and aPL antibodies. Further studies are needed to elucidate the role of complement deposition on platelets in development of venous thrombosis.
authors.affiliation: Department of Clinical Sciences Lund, Section of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Lood
authors.affiliation: Department of Clinical Sciences Lund, Section of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Tydén
authors.affiliation: Department of Laboratory Medicine Lund, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Gullstrand
authors.affiliation: Department of Clinical Sciences Lund, Section of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sturfelt
authors.affiliation: Department of Clinical Sciences Lund, Section of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jönsen
authors.affiliation: Department of Laboratory Medicine Lund, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.affiliation: Department of Clinical Sciences Lund, Section of Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Anders A
authors.initials: AA
authors.lastname: Bengtsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology; D003167:Complement Activation / Q000276:immunology*; D015935:Complement C4b / Q000276:immunology; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D015539:Platelet Activation / Q000276:immunology*; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000276:immunology; D055815:Young Adult
chemical_list: D017152:Antibodies, Antiphospholipid; D002308:Cardiolipins; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d