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Vascular events in autoantibody-defined clusters of SLE: a 12-year prospective cohort study

Sara Ferrigno1,2, Elizabeth V Arkema3, Iva Gunnarsson1

  • 1Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Rheumatology (Oxford, England)
|February 12, 2026
PubMed

Insights

Systemic lupus erythematosus (SLE) patients have varying cardiovascular and venous thromboembolism risks based on autoantibody profiles. The antiphospholipid antibody (aPL) cluster shows the highest risk, while the autoantibody-negative cluster has the lowest.

Area of Science:

  • Rheumatology
  • Immunology
  • Cardiology

Background:

  • Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations.
  • Autoantibody profiles are crucial for understanding SLE heterogeneity and predicting disease outcomes.
  • Cardiovascular events and venous thromboembolism are significant morbidities in SLE patients.

Purpose of the Study:

  • To investigate the incidence of major cardiovascular events (MACE) and venous thromboembolism (VTE) in SLE patients.
  • To stratify SLE patients into four distinct clusters based on 13 autoantibodies.
  • To compare vascular event incidence across these SLE autoantibody clusters and matched controls.

Main Methods:

  • Prospective cohort study of 461 SLE patients followed for 12.2 years.
  • Patients stratified into four baseline autoantibody clusters: Cluster 1 (anti-SSA/SSB), Cluster 2 (anti-nucleosome/Sm/RNP/dsDNA), Cluster 3 (aPL), and Cluster 4 (autoantibody-negative).
  • Vascular outcomes (MACE, VTE) prospectively retrieved via National Patient Register; Cox proportional hazards models used for risk estimation against 10 matched controls per patient.

Main Results:

  • The antiphospholipid antibody (aPL)-dominated cluster (Cluster 3) exhibited the highest relative risk for MACE (HR 1.91) and VTE (HR 2.69) compared to reference clusters.
  • Cluster 2 also showed elevated risks for heart failure and VTE, comparable to Cluster 3, despite patients being younger.
  • The autoantibody-negative cluster (Cluster 4) demonstrated the lowest incidence of vascular events among all SLE clusters.

Conclusions:

  • Significant differences in MACE and VTE incidence exist among SLE patients categorized by autoantibody profiles.
  • The aPL-dominated cluster is associated with the highest risk of major vascular events.
  • The autoantibody-negative SLE cluster is linked to the lowest vascular event incidence, highlighting the prognostic value of autoantibody profiling.
Abstract

Keywords:
SLEautoantibodiescardiovascular eventscluster analysisincidence ratethromboembolic events

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