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Vascular damage in systemic lupus erythematosus
William G Ambler1, Mariana J Kaplan2
1Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Insights
Systemic lupus erythematosus (SLE) accelerates vascular disease through immune dysregulation, particularly involving type 1 interferon (IFN-I) and neutrophils. Understanding these mechanisms is crucial for developing new treatments for SLE patients and common cardiovascular diseases.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Rheumatology
Background:
- Vascular disease is a primary cause of death in systemic lupus erythematosus (SLE).
- Standard cardiovascular risk factors do not fully account for the high incidence of premature vascular disease in SLE patients.
- Immune system dysregulation is the main driver of accelerated vascular damage in SLE.
Purpose of the Study:
- To investigate the roles of type 1 interferon (IFN-I) and neutrophils in the pathogenesis of vascular damage in SLE.
- To explore potential therapeutic targets for preventing and treating vascular complications in SLE.
Main Methods:
- Review of existing literature on the immunological mechanisms of vascular damage in SLE.
- Analysis of the effects of IFN-I on endothelial cells and immune cells.
- Examination of the role of neutrophil extracellular traps (NETs) in SLE-associated vasculopathy.
Main Results:
- Type 1 interferon (IFN-I) directly and indirectly promotes endothelial dysfunction.
- SLE neutrophils exhibit increased formation of immunostimulatory neutrophil extracellular traps (NETs), contributing to vasculopathy.
- Immune dysregulation, especially involving IFN-I and neutrophils, is central to accelerated vascular injury in SLE.
Conclusions:
- Dysregulation of IFN-I and aberrant neutrophils are key players in SLE vascular disease pathogenesis.
- Targeting these immune pathways may offer new therapeutic strategies for SLE patients.
- Understanding SLE vascular injury mechanisms could inform treatments for common cardiovascular diseases like atherosclerosis and hypertension.
Abstract:
Vascular disease is a major cause of morbidity and mortality in patients with systemic autoimmune diseases, particularly systemic lupus erythematosus (SLE). Although comorbid cardiovascular risk factors are frequently present in patients with SLE, they do not explain the high burden of premature vascular disease. Profound innate and adaptive immune dysregulation seems to be the primary driver of accelerated vascular damage in SLE. In particular, evidence suggests that dysregulation of type 1 interferon (IFN-I) and aberrant neutrophils have key roles in the pathogenesis of vascular damage. IFN-I promotes endothelial dysfunction directly via effects on endothelial cells and indirectly via priming of immune cells that contribute to vascular damage. SLE neutrophils are vasculopathic in part because of their increased ability to form immunostimulatory neutrophil extracellular traps. Despite improvements in clinical care, cardiovascular disease remains the leading cause of mortality among patients with SLE, and treatments that improve vascular outcomes are urgently needed. Improved understanding of the mechanisms of vascular injury in inflammatory conditions such as SLE could also have implications for common cardiovascular diseases, such as atherosclerosis and hypertension, and may ultimately lead to personalized therapeutic approaches to the prevention and treatment of this potentially fatal complication.
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