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.
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