Session Title: Systemic Lupus Erythematosus: Clinical Aspects
Session Type: Abstract Submissions (ACR)
Background/Purpose: Systemic Lupus Erythematosus (SLE) is associated with an increased risk of clinical and subclinical cardiovascular disease (CVD) including endothelial dysfunction, in part due to systemic inflammatory disease activity. Endothelial microparticles (EMPs) are membrane-bound subcellular particles produced by endothelial cells in response to a variety of activation triggers, including inflammatory cytokines and classic CVD risk factors. EMPs reflect endothelial damage and may correlate with measures of endothelial function, such as flow-mediated dilatation (FMD) of the brachial artery. EMPs may therefore serve as a biomarker for endothelial dysfunction in SLE. We aimed to: 1) compare EMP levels and FMD in patients with active SLE compared to controls; 2) assess change over time in EMP and FMD following improved disease control and 3) assess the correlation between EMPs and FMD.
Methods: Patients with active SLE (≥4 ACR criteria) were recruited and assessed at baseline and 4 months after a change in therapy. Disease activity (BILAG 2004 and SLEDAI 2K) and clinical features were recorded at each visit. Healthy age-matched controls were assessed once. FMD (%) of the brachial artery was measured using 2D ultrasound and automated edge-tracking software. EMPs were quantified (number/ml) using flow cytometry after incubating platelet-poor-plasma with the cell surface markers CD31, CD42b and Annexin-V. Events positive for annexin-V and CD31, and negative for CD42b, were classified as EMPs. Continuous data were compared using Mann-Whitney test, and Spearman’s Rank was used to correlate EMP levels with %FMD.
Results: 27 patients with SLE (mean (SD) age 41.5 (14.1) yrs) and 22 controls (mean age (SD) 38.5 (9.3) yrs) underwent assessment of endothelial function. In SLE patients the mean (SD) SLEDAI-2K and total BILAG scores were 8.2 (5.5) and 16.9 (10.6) respectively. Endothelial-dependent FMD was significantly reduced in the SLE group compared to controls at baseline (median (IQR) FMD 1.63% (-1.22, 5.32) vs. 5.40% (3.02, 8.57); p = 0.05). EMPs (n/ml) were significantly elevated in the SLE cohort compared to controls at baseline (median (IQR) 157,548/ml (59,906, 272,643) vs. 41,025 (30,179, 98,082); p = 0.003). In patients with paired results, disease activity significantly improved 4 months after a change in therapy (SLEDAI-2K 3.8 (3.4); BILAG 2004 score 6.9 (5.4) (p= 0.001 and 0.001 vs. baseline respectively). The median (IQR) FMD improved over time (0.33% (-2.31, 4.1) vs. 3.19% (0.98, 5.09); p = 0.1), as did median (IQR) EMP levels (166,982/ml (59906, 278,775 vs. 55655 (29475, 188,659; p = 0.02). In the whole cohort, EMPs demonstrated a significant negative correlation with %FMD (correlation coefficient -0.42; p =0.008). In SLE patients with paired data the correlation coefficient was -0.51 (p = 0.005).
Conclusion: Endothelial function is significantly impaired and EMPs are significantly elevated in young patients with active SLE compared to healthy controls. Both EMPs and FMD improve over time, following a reduction in disease activity. EMPs also correlate with FMD, and may serve as a useful biomarker of endothelial damage/dysfunction and CVD risk in SLE.
M. Y. Alexander,
I. N. Bruce,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/endothelial-microparticles-as-a-biomarker-for-endothelial-dysfunction-in-active-systemic-lupus-erythematosus/