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Venous thromboembolism (VTE) is a common thrombotic vascular condition, comprising deep venous thrombosis-DVT and pulmonary embolism-PE. PE has a mortality rate of >15% in the first 3 months after diagnosis. Many studies show that patients with rheumatic diseases have an increased risk for cardiovascular disease. Comparatively little is known about the VTE-risk in rheumatic disorders. Despite the suggestive mechanistic links between systemic autoimmune diseases and VTEs, these highly inflammatory conditions are under-recognized as risk factors for hypercoagulability, and the underlying mechanisms explaining the increased risk for VTEs have not been clarified. We aim to identify, understand and eventually treat the underlying causes for VTE in consecutive cohorts of patients with ANCA-associated vasculitis (AAV), antiphospholipid syndrome (APS), systemic sclerosis (SSc), rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The cross-talk between the coagulation, fibrinolysis and inflammation will be studied by investigating endothelial activation, the levels and activity of extracellular vesicles, thrombin generation, fibrin formation, fibrinolyisis and fibrin clot structure in relation to complement activation and inflammatory markers. In this way we would be able to link different steps of hemostatic process with inflammatory response and clinical characteristics of patients with AAV, APS, SSc, RA and PsA. Performing all analysis simultaneously in a single plasma sample comprises the investigation of virtually all components of hemostais without the need to analyse the whole blood. Identifying clinical- and laboratory characteristics of patients at VTE-risk among patients with AAV, APS, SSc, RA and PsA has important consequences in terms of management and treatment

one might speculate that an addition of anticoagulant treatment to the aggressive anti-inflammatory treatment during flares could remodel vascular involvement especially in early stages of these diseases. The knowledge and clinical experience from this project should lead to favorable prognosis for individual patients.

SLE is a heterogeneous autoimmune disease, characterized by the production of autoantibodies. Vascular disease (VD) is a major cause of early morbidity and mortality. Based on clinical experience and unsupervised clustering of 13 clinically relevant autoantibodies in 911 patients, we identified 4 SLE subgroups. Roughly outlined below:Anti-SSA/SSB, skin manifestations, Sjogren’s syndrom, HLA-DRB1*03Anti- dsDNA/nucleosome/Sm, nephritis, enhanced atherosclerosis, early onset, HLA-DRB1*15aPL, clotting disorders, HLA-DRB1*04No autoantibodies, late onset, no HLA association.Aim: To identify mechanisms contributing to autoimmunity and VD, by analyses of the 4 SLE subgroups separately.Method: We have since 1995 followed well-characterized cohorts, comprising &gt

800 SLE, and 320 controls, every 10 years. Follow-up is ongoing at the clinic and in the National Patient Registries (NPR), where we also identify all Swedish SLE patients (N=7000) and 10 controls/patient.We seek to determine if the 4 groups differ regarding:Proteomics, new autoantibodies and microparticles (vesicles of cellular origin).Blood samples drawn during the different menstrual phases in women with SLE (new approach).Vascular function in the heart, as determined by cardiac magnetic resonance investigation.VD and long-term outcomes in NPRSignificance: Our results can impact how we diagnose and treat SLE in the future. VD mainly affects groups 2 and 3 but by different mechanisms, calling for tailored preventive treatment.