# Immunopathogenesis of accelerated atherosclerosis in systemic lupus erythematosus: from innate and adaptive dysregulation to clinical implications

## TL;DR

This paper reviews how immune system dysregulation in lupus leads to faster atherosclerosis and higher heart disease risk.

## Contribution

The paper provides a comprehensive review of immune mechanisms linking systemic lupus erythematosus to accelerated atherosclerosis.

## Key findings

- Aberrant interferon signaling and neutrophil dysfunction form a feedback loop that worsens atherosclerosis.
- Dysfunctional innate immune cells and complement activation contribute to vascular injury in lupus patients.
- B-cell autoantibodies and imbalanced T-cells promote inflammation and atherosclerosis progression.

## Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with significantly accelerated atherosclerosis (AS) and increased cardiovascular risk. This review elucidates the complex immunopathological mechanisms through which SLE promotes AS, involving both innate and adaptive immune dysregulation. Aberrant activation of the type I interferon signaling pathway and dysfunctional neutrophil/NETosis reciprocally amplify each other, forming a core upstream positive feedback loop. This loop accelerates atherosclerosis progression through multiple pathways, including driving endothelial dysfunction, promoting foam cell formation, and undermining plaque stability. Dysregulation of innate immune cells is prominent. Monocytes and macrophages exhibit altered polarization and impaired efferocytosis. Complement activation further exacerbates vascular injury. Within the adaptive immune system, T-cell subsets are imbalanced, promoting inflammation and AS progression. B cells and autoantibodies play dual roles. Although certain natural IgM antibodies may be protective, class-switched IgG autoantibodies often promote atherosclerosis. The role of B-cell activating factor (BAFF) and its inhibition in AS remains complex and context dependent. Animal models have been instrumental in dissecting these pathways, revealing interactions between lupus-like autoimmunity and atherogenic processes. Despite these advances, accurately assessing cardiovascular risk in SLE patients remains challenging, underscoring the need for SLE-specific risk prediction tools. Future directions should focus on identifying specific immune mechanisms, developing targeted immunomodulatory therapies, and establishing improved risk stratification strategies to enable early intervention and improve long-term outcomes for patients with SLE.