从反映血管内皮细胞激活的血清标志物中学习：儿童发病系统性红斑狼疮的纵向数据。

Learning from serum markers reflecting endothelial activation: longitudinal data in childhood-onset systemic lupus erythematosus.

机构信息

Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centres (AUMC), University of Amsterdam, Amsterdam, The Netherlands

Amsterdam Institute for Molecular and Life Sciences (AIMMS), Division of Medicinal Chemistry, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

出版信息

Lupus Sci Med. 2024 Sep 5;11(2):e001190. doi: 10.1136/lupus-2024-001190.

DOI:10.1136/lupus-2024-001190

PMID:39242108

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11381702/

Abstract

OBJECTIVES

In childhood-onset SLE (cSLE), patients have an increased risk of premature atherosclerosis. The pathophysiological mechanisms for this premature atherosclerosis are not yet completely understood, but besides traditional risk factors, the endothelium plays a major role. The first aim of this study was to measure levels of SLE-associated markers involved in endothelial cell (EC) function and lipids in a cSLE cohort longitudinally in comparison with healthy controls (HC). Next aim was to correlate these levels with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and nailfold capillaroscopic patterns.

METHODS

Blood serum samples, videocapillaroscopy images and patient characteristics were collected in a multicentre longitudinal cSLE cohort and from age and sex comparable HC. Disease activity was evaluated by SLEDAI. A total of 15 EC markers and six lipids were measured in two longitudinal cSLE samples (minimum interval of 6 months) and in HC. Nailfold videocapillaroscopy images were scored according to the guidelines from the EULAR Study Group on Microcirculation in Rheumatic Diseases.

RESULTS

In total, 47 patients with cSLE and 42 HCs were analysed. Median age at diagnosis was 15 years (IQR 12-16 years). Median time between t=1 and t=2 was 14.5 months (IQR 9-24 months). Median SLEDAI was 12 (IQR 6-18) at t=1 and 2 (IQR 1-4) at t=2. Serum levels of angiopoietin-2, CCL2, CXCL10, GAS6, pentraxin-3, thrombomodulin, VCAM-1 and vWF-A2 were elevated in cSLE compared with HC at t=1. While many elevated EC markers at t=1 normalised over time after treatment, several markers remained significantly increased compared with HC (angiopoietin-2, CCL2, CXCL10, GAS6, thrombomodulin and VCAM-1).

CONCLUSION

In serum from patients with cSLE different markers of endothelial activation were dysregulated. While most markers normalised during treatment, others remained elevated in a subset of patients, even during low disease activity. These results suggest a role for the dysregulated endothelium in early and later phases of cSLE, possibly also during lower disease activity.

TRIAL REGISTRATION NUMBER

NL60885.018.17.

摘要

目的

在儿童起病的系统性红斑狼疮（cSLE）中，患者存在过早发生动脉粥样硬化的风险增加。这种过早发生动脉粥样硬化的病理生理机制尚不完全清楚，但除了传统的危险因素外，内皮细胞也起着重要作用。本研究的第一个目的是在与健康对照组（HC）进行比较的情况下，纵向测量 cSLE 队列中与 SLE 相关的内皮细胞（EC）功能和脂质标志物的水平。第二个目的是将这些水平与系统性红斑狼疮疾病活动指数（SLEDAI）和甲襞毛细血管镜模式相关联。

方法

在一个多中心的 cSLE 纵向队列中收集血清样本、视频毛细血管镜图像和患者特征，并从年龄和性别相匹配的 HC 中收集。通过 SLEDAI 评估疾病活动。在两个 cSLE 样本（最短间隔 6 个月）和 HC 中测量了 15 种 EC 标志物和 6 种脂质。根据 EULAR 微血管研究组的指南对甲襞视频毛细血管镜图像进行评分。

结果

共分析了 47 例 cSLE 患者和 42 例 HC。诊断时的中位年龄为 15 岁（IQR 12-16 岁）。中位 t=1 至 t=2 的时间为 14.5 个月（IQR 9-24 个月）。t=1 时的中位 SLEDAI 为 12（IQR 6-18），t=2 时为 2（IQR 1-4）。与 t=1 时的 HC 相比，cSLE 患者的血管生成素-2、CCL2、CXCL10、GAS6、Pentraxin-3、血栓调节蛋白、VCAM-1 和 vWF-A2 的血清水平升高。尽管许多在 t=1 时升高的 EC 标志物在治疗后随时间正常化，但一些标志物与 HC 相比仍显著升高（血管生成素-2、CCL2、CXCL10、GAS6、血栓调节蛋白和 VCAM-1）。