The goal of this observational study is to investigate different phenotypes among patients with SLE and to compare with matched general population controls. The main questions we aim to answer are:

A To investigate if subgroups of patients with systemic lupus erythematosus (SLE) defined by autoantibodies, genetic predisposition or biomarkers, rather than the present diagnostic entities account for the high risk of premature vascular disease.

B To perform in depth studies of selected patient groups to shed light on the autoimmune mechanisms behind antiphospholipid (aPL) antibodies and nephritis and their association to vascular disease in SLE and APS Participants will be investigated in person by a nurse and a rheumatologist. Data on previous and present disease characteristics, anthropometric measurements and health related quality of life (according to selfreported questionnaires) will be entered into a data base. Blood samples (plasma serum and DNA), urine and saliva is stored in a corresponding biobank.

Researchers will compare identified subgroups of SLE patients to each other and to matched population controls.

The clinical base for this application is a series of cross-sectional studies, performed every 10 years, including all consenting SLE patients at Rheumatology Karolinska. The first studies were initiated 1995-99, with second follow-up 2004-14. Since 2015, a third follow-up of prevalent and new cases is ongoing (presently comprising 400 patients, inclusions have been temporarily slowed by the Covid-19 pandemic). Very detailed clinical characterization, lifestyle questionnaires, together with results from carotid ultrasound and bone mineral density measures have been tabulated. General disease activity as well as features of lupus nephritis, and detailed autoantibody profiles are recorded at inclusion. Samples (plasma, serum, DNA, urine and saliva) are stored. We have a common database for the three cross-sectional studies. The total number of well-characterized SLE patients in these studies is today 867 SLE patients and >250 APS patients.

Population based controls identified in the national population registry (NPR), individually matched for age, sex, and residency have been investigated in person according to the same structured protocol (n=320). New controls will be included to match the "2015+ study".

Inclusion Criteria:

SLE according to criteria (ACR82 or SLICC 2012) and consenting to participate

Exclusion Criteria:

Not possible to read and understand patient information due to language barriers or psychological/psychiatric disorders Not consenting

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SLE patients as described above who are cared for at karolinska University Hospital, Danderyds Hospital or Center forRheumathology (CFR) in Stockholm and matched general population controls

Clinical and autoantibody data collected at inclusion

July 15 2025 until July 15 2027

Selected data will be shared with Christian Lood, University of Washington USA, using Managed File Transfer at Karolinska Institutet.