NIH Research Festival
Patients with systemic lupus erythematosus (SLE) show a striking increase in risk of atherosclerotic cardiovascular disease (CVD) not explained by Framingham risk (FR). Immune dysregulation associated with aberrant neutrophils (low density granulocytes, LDGs) and neutrophil extracellular traps (NETs) may play key roles in conferring enhanced CVD risk. Whether neutrophils predict vascular inflammation remains to be determined. SLE patients, compared to age and gender-matched controls, underwent assessment of a) vascular function of various arterial territories (peripheral arterial tonometry of microvasculature (Endopat) and arterial compliance by CAVI); b) aortic inflammation by FDG-PET/CT; and c) anatomical assessment of plaque by coronary CT angiogram. Circulating LDGs were quantified by flow cytometry and NET products in plasma were quantified by ELISA. Lupus(n=20) and healthy controls(n=15) did not differ in age, gender, ethnicity, FR, or insulin resistance. Median disease duration was 20.5 years (IQR 9.3-54 years) and SLEDAI was 2+4.8. Arterial stiffness assessed by CAVI was increased in SLE (CAVI:7.24[5.6-9.3]) vs. controls (6.53[5.1-8.3];p=0.03) and by Endopat augmentation index (AI:25.7[0.05-78.9]) vs. controls (6.81[-17.4-55.4],p=0.003). Differences in control and SLE persisted in multivariate regression analysis beyond adjustment for cardiovascular and cardiometabolic risk factors. LDGs and plasma NET products were elevated in SLE and associated with enhanced arterial inflammation and noncalcified plaque burden. Individuals with SLE demonstrate increased arterial stiffness and arterial inflammation suggestive of risk for unstable plaque. Dysregulation in neutrophil function and NETosis occurs in vivo in SLE in association with arterial inflammation and vascular dysfunction, indicating neutrophils may be important drivers of vascular damage in SLE.
Scientific Focus Area: Immunology
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