Subgrouping SLE - a new approach to understand the pathogenesis and improve treatment

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 >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.