Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers.
Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers.
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DOI：
10.1136/thoraxjnl-2020-215356
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发表时间：
2021-04
期刊：
影响因子：
10
通讯作者：
Sciurba FC
中科院分区：
文献类型：
--
作者：
Zhang Y;Tedrow J;Nouraie M;Li X;Chandra D;Bon J;Kass DJ;Fuhrman CR;Leader JK;Duncan SR;Kaminski N;Sciurba FC
正五聚蛋白3（PTX3）影响先天免疫和炎症、宿主防御、补体级联反应和血管生成。烟草暴露受试者肺和血液中PTX 3的表达及其与疾病模式和临床结果的潜在关系尚不清楚。使用独立的平台和队列，我们确定了当前和以前吸烟者（有和没有慢性阻塞性肺疾病，COPD）的肺组织和血浆中PTX 3基因表达与疾病表型的相关性，包括定量CT确定的肺气肿，肺功能，症状和生存率。研究了PTX3基因的两种假定的调节变体与COPD表现的相关性。进一步检查血浆PTX 3和透明质酸水平之间的关系。肺组织中PTX 3基因表达与肺气肿严重程度直接相关（p<0.0001）。PTX 3的循环水平与FEV1呈负相关（p=0.006），与肺气肿严重程度（p=0.004）和死亡率（p=0.008）呈正相关。两种PTX 3基因调控变异与肺气肿和呼气气流阻塞的风险降低相关，并且PTX 3和透明质酸的血浆水平相关。这些数据显示，肺和血液PTX 3水平以及PTX 3调节基因变异与吸烟者气流阻塞、肺气肿和死亡率的严重程度存在强烈的重叠相关性。这些发现对吸烟相关肺部疾病的发病机制具有潜在意义，并保证进一步探索使用PTX 3作为预测生物标志物。
Pentraxin 3 (PTX3) influences innate immunity and inflammation, host defence, the complement cascade and angiogenesis. PTX3 expression in lung and blood of subjects with tobacco exposure, and its potential relationship with disease pattern and clinical outcome are poorly understood. Using independent platforms and cohorts, we identified associations of PTX3 gene expression in lung tissue and plasma from current and former tobacco smokers (with and without chronic obstructive pulmonary disease, COPD) to disease phenotypes including quantitative CT determined emphysema, lung function, symptoms and survival. Two putative regulatory variants of the PTX3 gene were examined for association with COPD manifestations. The relationship between plasma PTX3 and hyaluronic acid levels was further examined. PTX3 gene expression in lung tissue was directly correlated with emphysema severity (p<0.0001). Circulating levels of PTX3 were inversely correlated with FEV1 (p=0.006), and positively associated with emphysema severity (p=0.004) and mortality (p=0.008). Two PTX3 gene regulatory variants were associated with a lower risk for emphysema and expiratory airflow obstruction, and plasma levels of PTX3 and hyaluronic acid were related. These data show strong and overlapping associations of lung and blood PTX3 levels, and PTX3 regulatory gene variants, with the severity of airflow obstruction, emphysema and mortality among smokers. These findings have potential implications regarding the pathogenesis of smoking-related lung diseases and warrant further exploration for the use of PTX3 as a predictive biomarker.
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影响因子：
3.7
作者：
Barbati E;Specchia C;Villella M;Rossi ML;Barlera S;Bottazzi B;Crociati L;d'Arienzo C;Fanelli R;Garlanda C;Gori F;Mango R;Mantovani A;Merla G;Nicolis EB;Pietri S;Presbitero P;Sudo Y;Villella A;Franzosi MG
通讯作者：
Franzosi MG
影响因子：
5.8
作者：
Pauwels NS;Bracke KR;Maes T;Van Pottelberge GR;Garlanda C;Mantovani A;Joos GF;Brusselle GG
通讯作者：
Brusselle GG
影响因子：
6.9
作者：
Ievoli, Elena;Lindstedt, Ragnar;Inforzato, Antonio;Camaioni, Antonella;Palone, Francesca;Day, Anthony J.;Mantovani, Alberto;Salvatori, Giovanni;Salustri, Antonietta
通讯作者：
Salustri, Antonietta
影响因子：
8.8
作者：
Mauri, Tommaso;Coppadoro, Andrea;Pesenti, Antonio
通讯作者：
Pesenti, Antonio
影响因子：
6.9
作者：
Garantziotis, Stavros;Savani, Rashmin C.
通讯作者：
Savani, Rashmin C.