Plasma markers in pulmonary hypertension subgroups correlate with patient survival.
Plasma markers in pulmonary hypertension subgroups correlate with patient survival.
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DOI：
10.1186/s12931-021-01716-w
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发表时间：
2021-05-04
影响因子：
5.8
通讯作者：
Boomars KA
中科院分区：
文献类型：
--
作者：
Koudstaal T;van Uden D;van Hulst JAC;Heukels P;Bergen IM;Geenen LW;Baggen VJM;van den Bosch AE;van den Toorn LM;Chandoesing PP;Kool M;Boersma E;Hendriks RW;Boomars KA
最近的研究提供了免疫系统在肺动脉高压（PAH）和慢性血栓栓塞性肺动脉高压（CTEPH）的病理生理中的重要贡献的证据。在本报告中，我们调查了肺动脉高压患者的炎症特征是否随时间而变化，并与患者WHO亚组或生存率相关。50例PAH患者(特发性(I)PAH 16例，结缔组织病（CTD)-PAH 24例，先天性心脏病(CHD)-PAH 10例），CTEPH 37例，健康对照（hc） 18例。在基线和1年随访后使用elisa检测血浆炎症标志物。随后，研究血流动力学参数与生存率的相关性，并对数据集进行无偏多变量分析。在诊断时，我们发现与hc相比，CTD-PAH患者血浆中白细胞介素-6 （IL-6）和趋化因子（C-X3-C）基序图示CXCL9和CXCL13的水平显著升高。与hcc相比，特发性PAH患者的肿瘤生长因子-β (TGFβ)、IL-10和CXCL9水平升高。CETPH患者中CXCL9和IL-8浓度升高与生存率降低显著相关，提示CXCL9和IL-8可能是预后指标。治疗一年后，PAH亚组和CTEPH患者IL-10、CXCL13和TGFβ水平发生显著变化。无偏多变量分析显示PH患者基于炎症介质和临床参数聚类，但没有分离WHO亚组。重要的是，这些多变量分析将生存期< 3年和< 3年的患者分开，特别是当炎症介质与临床参数相结合时。我们的研究显示，在基线和1年随访中，不同PAH亚组和CTEPH的炎症介质血浆水平升高，因此CXCL9和IL-8可能被证明是CTEPH患者的预后标志物。虽然这项研究是探索性的和假设性的，但我们的数据表明IL-8和CXCL9在冠心病和CTEPH患者中具有重要作用，考虑到血浆水平升高以及观察到的与生存率的相关性。总之，我们的研究确定了一种炎症特征，将PH患者聚集到与世卫组织分类无关的亚组中，这些亚组与患者生存率相关。在线版本包含补充材料，可在10.1186/s12931-021-01716-w获得。
Recent studies have provided evidence for an important contribution of the immune system in the pathophysiology of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we investigated whether the inflammatory profile of pulmonary hypertension patients changes over time and correlates with patient WHO subgroups or survival. 50 PAH patients (16 idiopathic (I)PAH, 24 Connective Tissue Disease (CTD)-PAH and 10 Congenital Heart Disease (CHD)-PAH), 37 CTEPH patients and 18 healthy controls (HCs) were included in the study. Plasma inflammatory markers at baseline and after 1-year follow-up were measured using ELISAs. Subsequently, correlations with hemodynamic parameters and survival were explored and data sets were subjected to unbiased multivariate analyses. At diagnosis, we found that plasma levels of interleukin-6 (IL-6) and the chemokines (C-X3-C) motif legend CXCL9 and CXCL13 in CTD-PAH patients were significantly increased, compared with HCs. In idiopathic PAH patients the levels of tumor growth factor-β (TGFβ), IL-10 and CXCL9 were elevated, compared with HCs. The increased CXCL9 and IL-8 concentrations in CETPH patients correlated significantly with decreased survival, suggesting that CXCL9 and IL-8 may be prognostic markers. After one year of treatment, IL-10, CXCL13 and TGFβ levels changed significantly in the PAH subgroups and CTEPH patients. Unbiased multivariate analysis revealed clustering of PH patients based on inflammatory mediators and clinical parameters, but did not separate the WHO subgroups. Importantly, these multivariate analyses separated patients with < 3 years and > 3 years survival, in particular when inflammatory mediators were combined with clinical parameters. Our study revealed elevated plasma levels of inflammatory mediators in different PAH subgroups and CTEPH at baseline and at 1-year follow-up, whereby CXCL9 and IL-8 may prove to be prognostic markers for CTEPH patients. While this study is exploratory and hypothesis generating, our data indicate an important role for IL-8 and CXCL9 in CHD and CTEPH patients considering the increased plasma levels and the observed correlation with survival. In conclusion, our studies identified an inflammatory signature that clustered PH patients into WHO classification-independent subgroups that correlated with patient survival. The online version contains supplementary material available at 10.1186/s12931-021-01716-w.
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影响因子：
24.3
作者：
Boucly, Athenais;Weatherald, Jason;Sitbon, Olivier
通讯作者：
Sitbon, Olivier
DOI：
10.1016/s0735-1097(86)80301-1
发表时间：
1986-12-01
影响因子：
24
作者：
RICH, S;KIERAS, K;BRUNDAGE, BH
通讯作者：
BRUNDAGE, BH
影响因子：
32.4
作者：
Groom JR;Richmond J;Murooka TT;Sorensen EW;Sung JH;Bankert K;von Andrian UH;Moon JJ;Mempel TR;Luster AD
通讯作者：
Luster AD
影响因子：
5.8
作者：
Le, Sebastien;Josse, Julie;Husson, Francois
通讯作者：
Husson, Francois
影响因子：
9.6
作者：
Benza, Raymond L.;Miller, Dave P.;McGoon, Michael D.
通讯作者：
McGoon, Michael D.