Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers

• Published in: Thorax Vol. 76; no. 4; pp. 335 - 342
• Main Authors: Zhang, Yingze, Tedrow, John, Nouraie, Mehdi, Li, Xiaoyun, Chandra, Divay, Bon, Jessica, Kass, Daniel J, Fuhrman, Carl R, Leader, Joseph K, Duncan, Steven R, Kaminski, Naftali, Sciurba, Frank C
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Thoracic Society 01.04.2021; BMJ Publishing Group LTD
• Subjects: Chronic obstructive pulmonary disease; COPD ÀÜ mechanisms; Deoxyribonucleic acid; DNA; Emphysema; Gene expression; Hyaluronic acid; Lung diseases; Lungs; Mortality; Plasma; Proteins; R&D; Regression analysis; Research & development; Smoking; Survival analysis; Tobacco; Transplants & implants; United States > US; Pittsburgh Pennsylvania; COPD ÀÜ mechanisms; emphysema
• ISSN: 0040-6376; 1468-3296; 1468-3296
• DOI: 10.1136/thoraxjnl-2020-215356

BackgroundPentraxin 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.MethodsUsing 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.Results 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.ConclusionsThese 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.