Circulating Levels of Low-Density Granulocytes and Cell-Free DNA as Predictors of Cardiovascular Disease and Bone...

Area of Science:

• Immunology
• Rheumatology
• Cardiology

Background:

• Systemic lupus erythematosus (SLE) is associated with increased cardiovascular disease (CVD) and bone deterioration (BD) risk.
• Low-density granulocytes (LDGs) play a role in SLE pathogenesis, potentially through neutrophil extracellular trap (NET) formation.
• Identifying reliable biomarkers for predicting CVD and BD in SLE patients is crucial for proactive management.

Purpose of the Study:

• To evaluate the predictive value of LDGs for the development of CVD and/or BD in a 6-year prospective study of SLE patients.
• To assess circulating cell-free DNA (cirDNA) levels, including mitochondrial (mtDNA) and nuclear DNA (nDNA), as potential LDG-associated biomarkers for CVD and BD risk in SLE.

Main Methods:

• Quantified LDGs and their subsets (nLDG, pLDG) using flow cytometry in 144 SLE patients and 33 controls.
• Measured total cirDNA, mtDNA, and nDNA concentrations in plasma via fluorometry or qPCR at study enrolment.
• Followed patients prospectively for 6 years to assess the incidence of CVD and BD.

Main Results:

• Increased blood levels of SLE-nLDGs at enrolment were associated with prospective CVD development (pCVD) and the presence of BD.
• Circulating DNA levels (total cirDNA, nDNA, mtDNA) were elevated in SLE patients, particularly those with traditional CV risk factors or subclinical atheromatosis.
• nDNA concentration demonstrated predictive value for pCVD development in SLE, similar to nLDGs.

Conclusions:

• LDG expansion is a significant predictor of both CVD and BD progression in SLE.
• Circulating nDNA levels can serve as a surrogate marker for LDGs, aiding in the clinical prediction of CVD risk in SLE patients.
• These findings highlight the potential of LDGs and cirDNA as valuable biomarkers for risk stratification and management of comorbidities in SLE.