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HDL Cholesterol Efflux and the Complement System Are Linked in Systemic Lupus Erythematosus
María García-González1, Fuensanta Gómez-Bernal2, Juan C Quevedo-Abeledo3
1Division of Rheumatology, Hospital Universitario de Canarias, 38320 Tenerife, Spain.
Insights
Cholesterol efflux capacity (CEC) is reduced in patients with systemic lupus erythematosus (SLE). Complement system activation, particularly the alternative pathway, negatively impacts CEC in SLE patients, highlighting a key link between these factors.
Area of Science:
- Immunology
- Cardiovascular Science
- Rheumatology
Background:
- Cholesterol efflux capacity (CEC) is crucial for preventing cardiovascular events.
- Systemic lupus erythematosus (SLE) is linked to increased cardiovascular disease risk and reduced CEC.
- Complement (C) system dysregulation is a hallmark of SLE.
Purpose of the Study:
- To investigate the influence of complement system disruption on CEC in SLE patients.
- To analyze the relationship between complement pathways and CEC in SLE.
Main Methods:
- Functional assays for the three complement pathways were performed in 207 SLE patients.
- Serum levels of complement molecules (inactive and activated) and regulators were measured.
- In vitro CEC assays and lipoprotein concentration assessments were conducted.
Main Results:
- The alternative complement cascade functional test showed a significant negative relationship with CEC.
- Complement C2 and C3 levels were positively and significantly associated with CEC after multivariable analysis.
- These findings indicate a significant interconnection between the complement system and CEC in SLE.
Conclusions:
- The complement system plays a significant role in modulating cholesterol efflux capacity in SLE.
- Understanding this interplay may offer new therapeutic targets for cardiovascular risk reduction in SLE patients.
Abstract:
Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL) cholesterol to accept cholesterol from macrophages, has been linked to cardiovascular events. Systemic lupus erythematosus (SLE) is characterized by the consumption of complement (C) proteins and has been associated with an increased risk of cardiovascular disease. CEC is reduced in SLE patients compared to controls. In the present work, our objective was to analyze whether the disruption of C influences CEC in patients with SLE. New-generation functional assays of the three pathways of the C system were performed in 207 patients with SLE. Additionally, serum levels of inactive (C1q, C2, C3, C4, and factor D) and activated (C3a) molecules, and regulators (C1-inhibitor and factor H) of C system were measured. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed. Multivariable linear regression analysis was performed to assess the relationship between C system and CEC. After full multivariable analysis, the alternative C cascade functional test showed a significant and negative relationship with CEC. This was also the case for C2 and C3, in which the associations were found to be positive and statistically significant, after adjustment for covariates. In conclusion, C system and CEC are interconnected in patients with SLE.
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