Background 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.
Methods 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.
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.
Conclusions 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.
- COPD ÀÜ mechanisms
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Twitter @yingzezhang, @kaminskimed
Deceased CRF: deceased
Contributors YZ, NK and FCS: study conceptualisation; YZ, NK, FCS and JT, experimental design; YZ, JT, XL, DC, JB, DJK, CRF, SRD, JKL, NK and FCS: data collection; YZ, JT, MN, NK and FCS: data quality control and analysis; YZ, SRD and FCS: manuscript writing; YZ, MN and FCS: manuscript revision; all authors: manuscript review.
Funding This study was funded by NIH NHLBI P50HL084948 (FCS), R21HL129917 (FCS/YZ), RC2 HL101715 (NK), HHSN268201100019C (FCS), HHSN2682016000071 (FCS), and Pennsylvania CURE SAP 4100062224 (FCS).
Competing interests NK reports personal fees from Biogen Idec, Boehringer Ingelheim, Third Rock, Pliant, Samumed, uMedii, Indaloo, Theravance, LifeMax, Three Lake Partners, RohBar; Non-financial support from Miragen and a research grant from Veracyte. NK has a patent New Therapies in Pulmonary Fibrosis and a patent on Peripheral Blood Gene Expression that is licensed to Biotech. All are outside this work.
Patient consent for publication Not required.
Ethics approval This study was approved by the Institutional Review Board for Human Subject Research at the University of Pittsburgh (STUDY19090239). All subjects provided written informed consent (in accordance with the Declaration of Helsinki).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. N/A.
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