Low-density granulocytes and monocytes as biomarkers of cardiovascular risk in systemic lupus erythematosus

Abstract

Objective The aim was to evaluate the most relevant cell populations involved in vascular homeostasis as potential biomarkers of SLE-related cardiovascular disease (CVD). Methods Low-density granulocytes (LDGs), monocyte subsets, endothelial progenitor cells, angiogenic T (Tang) cells, CD4+CD28null and Th1/Th17 lymphocytes and serum cytokine levels were quantified in 109 SLE patients and 33 controls in relationship to the presence of subclinical carotid atheromatosis or cardiovascular disease. A second cohort including 31 recent-onset SLE patients was also included. Results Raised monocyte and LDG counts, particularly those LDGs negative for CD16/CD14 expression (nLDGs), in addition to the ratios of monocytes and nLDGs to high-density lipoprotein-cholesterol (HDLc) molecules (MHR and nLHR, respectively), were present in SLE patients with traditional risk factors or subclinical atheromatosis but not in those who were CV-free, thus revealing their value in the identification of patients at risk of CVD, even at the onset of disease. Accordingly, nLDGs were correlated positively with carotid intima–media thickness (cIMT) and with inflammatory markers (CRP and IL-6). A bias towards more differentiated monocyte subsets, related to increased IFN-α and IL-17 serum levels, was also observed in patients. Intermediate monocytes were especially expanded, but independently of their involvement in CVD. Finally, CD4+CD28null, Th17 and Th1 lymphocytes were increased, with CD4+CD28null and Th17 cells being associated with cIMT, whereas endothelial progenitor and Tang cell levels were reduced in all SLE patients. Conclusion The present study highlights the potential use of MHR and nLHR as valuable biomarkers of CVD risk in SLE patients, even at diagnosis. The increased amounts of nLDGs, monocytes, Th17 and senescent-CD28null subsets, coupled with reduced pro-angiogenic endothelial progenitor cells and Tang cells, could underlie the development of atheromatosis in SLE.

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

“…Likewise, the monocyte to HDL ratio was positively correlated with c-reactive protein, IL-6 and carotid IMT in SLE patients with subclinical CVD but not those free of CVD. The ratio was adequate and comparable to carotid IMT in differentiating SLE patients at high risk for CVD [129]. Monocytes are a major source of proinflammatory species and key in potentiating atherogenesis, whereas HDL exhibits anti-atherosclerotic effects by neutralizing the proinflammatory and pro-oxidant effects of monocytes [130].…”

The potential roles of type I interferon activated neutrophils and neutrophil extracellular traps (NETs) in the pathogenesis of primary Sjögren’s syndrome

“…We also used CD14 lo/- CD15 + as markers for LDG identification (Fig. 4 C) [ 19 ] and found significantly elevated proportion of LDGs in PBMCs of pSS patients (0.95±0.27% vs 0.24±0.05%, P =0.014, Fig. 4 C), with the significantly increasing ROS production than normal density neutrophils (Figure S 3 A-B).…”

Accumulation of CD28null Senescent T-Cells Is Associated with Poorer Outcomes in COVID19 Patients

“…These CD4 + CD28 null cells express higher levels of pro-inflammatory and cytotoxic mediator than CD4 + CD28 + cells, strengthening their role in mediating the early development of atherosclerosis [53]. Recent studies on patients with rheumatoid arthritis (RA) and systemic lupus erythematosus echo these results: expansion of CD4 + CD28 null cells correlates with significantly higher carotid-intima media thickness and lower brachial artery flow-mediated endothelium-dependent dilation [54,77]. Moreover, CD4 + CD28 null cells are also a risk factor for poorer prognostic outcomes in CVD [57,58].…”