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

IF 3.7 2区医学 Q1 RHEUMATOLOGY

Lupus Science & Medicine Pub Date : 2024-09-05 DOI:10.1136/lupus-2024-001190

Sandy C Bergkamp, Nick D Bergkamp, Mohamed Javad Wahadat, Mariken P Gruppen, Amara Nassar-Sheikh Rashid, Sander W Tas, Martine J Smit, Marjan A Versnel, J Merlijn van den Berg, Sylvia Kamphuis, Dieneke Schonenberg-Meinema

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引用次数: 0

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.

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从反映内皮激活的血清标志物中学习：儿童期系统性红斑狼疮的纵向数据。

目的：儿童期发病的系统性红斑狼疮（cSLE）患者过早发生动脉粥样硬化的风险增加。这种过早动脉粥样硬化的病理生理机制尚未完全明了，但除了传统的风险因素外，内皮也起着重要作用。这项研究的第一个目的是测量系统性红斑狼疮相关标记物的水平，这些标记物与内皮细胞（EC）功能和血脂有关，并与健康对照组（HC）进行纵向比较。下一个目的是将这些标记物水平与系统性红斑狼疮疾病活动指数（SLEDAI）和甲皱毛细血管镜模式相关联：方法：在一个多中心纵向系统性红斑狼疮队列中收集血清样本、视频毛细血管镜图像和患者特征，并从具有年龄和性别可比性的HC中收集血清样本、视频毛细血管镜图像和患者特征。疾病活动性由 SLEDAI 评估。在两个纵向系统性红斑狼疮样本（最少间隔 6 个月）和 HC 中总共测量了 15 种 EC 标记物和 6 种血脂。根据 EULAR 风湿性疾病微循环研究小组的指导原则，对指甲折叠视频毛细血管镜图像进行评分：结果：共分析了 47 名 cSLE 患者和 42 名 HCs 患者。诊断时的中位年龄为 15 岁（IQR 12-16 岁）。t=1和t=2之间的中位时间为14.5个月（IQR为9-24个月）。t=1 时，SLEDAI 中位数为 12（IQR 6-18），t=2 时，SLEDAI 中位数为 2（IQR 1-4）。与HC相比，cSLE患者血清中血管生成素-2、CCL2、CXCL10、GAS6、五肽-3、血栓调节蛋白、VCAM-1和vWF-A2的水平在t=1时升高。治疗后，许多在t=1时升高的EC标记物随着时间的推移趋于正常，但有几种标记物（血管生成素-2、CCL2、CXCL10、GAS6、血栓调节蛋白和VCAM-1）与HC相比仍显著升高：结论：在系统性红斑狼疮患者的血清中，不同的内皮活化标志物出现了失调。虽然大多数标志物在治疗过程中恢复正常，但在一部分患者中，其他标志物仍在升高，即使在疾病活动较低时也是如此。这些结果表明，失调的内皮在系统性红斑狼疮的早期和晚期都有作用，在疾病活动较低时也有可能：试验注册号：NL60885.018.17。

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来源期刊

Lupus Science & Medicine RHEUMATOLOGY-

CiteScore

5.30

自引率

7.70%

发文量

审稿时长

15 weeks

期刊介绍： Lupus Science & Medicine is a global, peer reviewed, open access online journal that provides a central point for publication of basic, clinical, translational, and epidemiological studies of all aspects of lupus and related diseases. It is the first lupus-specific open access journal in the world and was developed in response to the need for a barrier-free forum for publication of groundbreaking studies in lupus. The journal publishes research on lupus from fields including, but not limited to: rheumatology, dermatology, nephrology, immunology, pediatrics, cardiology, hepatology, pulmonology, obstetrics and gynecology, and psychiatry.