Lemmers Jacqueline Mj, van Caam Arjan Pm, Kersten Brigit, van den Ende Cornelia Hm, Knaapen Hanneke, van Dijk Arie Pj, Hagmolen Of Ten Have Wanda, van den Hoogen Frank Hj, Koenen Hans, van Leuven Sander I, Alkema Wynand, Smeets Ruben L, Vonk Madelon C
Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Laboratory of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
J Scleroderma Relat Disord. 2023 Oct;8(3):221-230. doi: 10.1177/23971983231175213. Epub 2023 May 22.
Pulmonary hypertension is one of the leading causes of death in systemic sclerosis. Early detection and treatment of pulmonary hypertension in systemic sclerosis is crucial. Nailfold capillaroscopy microscopy, vascular autoantibodies AT1R and ETAR, and several candidate-biomarkers have the potential to serve as noninvasive tools to identify systemic sclerosis patients at risk for developing pulmonary hypertension. Here, we explore the classifying potential of nailfold capillaroscopy microscopy characteristics and serum levels of selected candidate-biomarkers in a sample of systemic sclerosis patients with and without different forms of pulmonary hypertension.
A total of 81 consecutive systemic sclerosis patients were included, 40 with systemic sclerosis pulmonary hypertension and 41 with no pulmonary hypertension. In each group, quantitative and qualitative nailfold capillaroscopy microscopy characteristics, vascular autoantibodies AT1R and ETAR, and serum levels of 24 soluble serum factors were determined. For evaluation of the nailfold capillaroscopy microscopy characteristics, linear regression analysis accounting for age, sex, and diffusing capacity of the lungs for carbon monoxide percentage predicted was used. Autoantibodies and soluble serum factor levels were compared using two-sample test with equal variances.
No statistically significant differences were observed in quantitative or qualitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibody ETAR and AT1R titer between systemic sclerosis-pulmonary hypertension and systemic sclerosis-no pulmonary hypertension. In contrast, several serum levels of soluble factors differed between groups: Endostatin, sVCAM, and VEGFD were increased, and CXCL4, sVEGFR2, and PDGF-AB/BB were decreased in systemic sclerosis-pulmonary hypertension. Random forest classification identified Endostatin and CXCL4 as the most predictive classifiers to distinguish systemic sclerosispulmonary hypertension from systemic sclerosis-no pulmonary hypertension.
This study shows the potential for several soluble serum factors to distinguish systemic sclerosis-pulmonary hypertension from systemic sclerosis-no pulmonary hypertension. We found no classifying potential for qualitative or quantitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibodies.
肺动脉高压是系统性硬化症的主要死亡原因之一。早期发现和治疗系统性硬化症中的肺动脉高压至关重要。甲襞毛细血管显微镜检查、血管自身抗体AT1R和ETAR以及几种候选生物标志物有潜力作为非侵入性工具，用于识别有发生肺动脉高压风险的系统性硬化症患者。在此，我们探讨甲襞毛细血管显微镜检查特征和选定候选生物标志物血清水平在有不同形式肺动脉高压和无肺动脉高压的系统性硬化症患者样本中的分类潜力。
共纳入81例连续的系统性硬化症患者，其中40例患有系统性硬化症相关性肺动脉高压，41例无肺动脉高压。在每组中，测定甲襞毛细血管显微镜检查的定量和定性特征、血管自身抗体AT1R和ETAR以及24种可溶性血清因子的血清水平。为评估甲襞毛细血管显微镜检查特征，使用了考虑年龄、性别和预测的肺一氧化碳弥散量百分比的线性回归分析。使用等方差双样本检验比较自身抗体和可溶性血清因子水平。
在系统性硬化症相关性肺动脉高压和无肺动脉高压的系统性硬化症患者之间，甲襞毛细血管显微镜检查的定量或定性特征、血管自身抗体ETAR和AT1R滴度均未观察到统计学显著差异。相比之下，几组可溶性因子的血清水平有所不同：在系统性硬化症相关性肺动脉高压中，内皮抑素、可溶性血管细胞黏附分子（sVCAM）和血管内皮生长因子D（VEGFD）升高，而CXC趋化因子配体4（CXCL4）、可溶性血管内皮生长因子受体2（sVEGFR2）和血小板衍生生长因子AB/BB（PDGF-AB/BB）降低。随机森林分类法确定内皮抑素和CXCL4是区分系统性硬化症相关性肺动脉高压和无肺动脉高压的系统性硬化症的最具预测性的分类器。
本研究显示了几种可溶性血清因子区分系统性硬化症相关性肺动脉高压和无肺动脉高压的系统性硬化症的潜力。我们未发现甲襞毛细血管显微镜检查的定性或定量特征或血管自身抗体具有分类潜力。
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