Human Pentraxin 3 (PTX3) as a Novel Biomarker for the Diagnosis of Pulmonary Arterial Hypertension

Yuichi Tamura, Tomohiko Ono, Masataka Kuwana, Kenji Inoue, Makoto Takei, Tsunehisa Yamamoto, Takashi Kawakami, Jun Fujita, Masaharu Kataoka, Kensuke Kimura, Motoaki Sano, Hiroyuki Daida, Toru Satoh, Keiichi Fukuda

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Abstract

Background: Although inflammation is an important feature of pulmonary arterial hypertension (PAH), the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested whether plasma concentrations of human pentraxin 3 (PTX3), a local inflammatory marker, would be a useful biomarker for detecting PAH. Methods: Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH), and six with congenital heart disease), 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) were also determined. Results: Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P<0.001). Using a threshold level of 2.84 ng/mL, PTX3 yielded a sensitivity of 74.0% and a specificity of 84.0% for the detection of PAH. In CTD-PAH patients, mean PTX3 concentrations were significantly higher than in CTD patients without PAH (5.02±0.69 vs. 2.40±0.14 ng/mL, respectively; P<0.001). There was no significant correlation between plasma levels of PTX3 and BNP or CRP. Receiver operating characteristic (ROC) curves for screening PAH in patients with CTD revealed that PTX3 (area under the ROC curve 0.866) is superior to BNP. Using a PTX3 threshold of 2.85 ng/mL maximized true-positive and false-negative results (sensitivity 94.1%, specificity 73.5%). Conclusion: Plasma concentrations of PTX3 may be a better biomarker of PAH than BNP, especially in patients with CTD.

Original languageEnglish
Article numbere45834
JournalPLoS One
Volume7
Issue number9
DOIs
Publication statusPublished - 2012 Sep 21

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Biomarkers
Pulmonary Hypertension
hypertension
biomarkers
lungs
Brain Natriuretic Peptide
natriuretic peptides
Plasmas
C-Reactive Protein
C-reactive protein
ROC Curve
PTX3 protein
Pulmonary diseases
Connective Tissue Diseases
Screening
heart diseases
Tissue
connective tissues
respiratory tract diseases
Heart Diseases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Human Pentraxin 3 (PTX3) as a Novel Biomarker for the Diagnosis of Pulmonary Arterial Hypertension. / Tamura, Yuichi; Ono, Tomohiko; Kuwana, Masataka; Inoue, Kenji; Takei, Makoto; Yamamoto, Tsunehisa; Kawakami, Takashi; Fujita, Jun; Kataoka, Masaharu; Kimura, Kensuke; Sano, Motoaki; Daida, Hiroyuki; Satoh, Toru; Fukuda, Keiichi.

In: PLoS One, Vol. 7, No. 9, e45834, 21.09.2012.

Research output: Contribution to journalArticle

Tamura, Y, Ono, T, Kuwana, M, Inoue, K, Takei, M, Yamamoto, T, Kawakami, T, Fujita, J, Kataoka, M, Kimura, K, Sano, M, Daida, H, Satoh, T & Fukuda, K 2012, 'Human Pentraxin 3 (PTX3) as a Novel Biomarker for the Diagnosis of Pulmonary Arterial Hypertension', PLoS One, vol. 7, no. 9, e45834. https://doi.org/10.1371/journal.pone.0045834
Tamura, Yuichi ; Ono, Tomohiko ; Kuwana, Masataka ; Inoue, Kenji ; Takei, Makoto ; Yamamoto, Tsunehisa ; Kawakami, Takashi ; Fujita, Jun ; Kataoka, Masaharu ; Kimura, Kensuke ; Sano, Motoaki ; Daida, Hiroyuki ; Satoh, Toru ; Fukuda, Keiichi. / Human Pentraxin 3 (PTX3) as a Novel Biomarker for the Diagnosis of Pulmonary Arterial Hypertension. In: PLoS One. 2012 ; Vol. 7, No. 9.
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abstract = "Background: Although inflammation is an important feature of pulmonary arterial hypertension (PAH), the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested whether plasma concentrations of human pentraxin 3 (PTX3), a local inflammatory marker, would be a useful biomarker for detecting PAH. Methods: Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH), and six with congenital heart disease), 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) were also determined. Results: Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P<0.001). Using a threshold level of 2.84 ng/mL, PTX3 yielded a sensitivity of 74.0{\%} and a specificity of 84.0{\%} for the detection of PAH. In CTD-PAH patients, mean PTX3 concentrations were significantly higher than in CTD patients without PAH (5.02±0.69 vs. 2.40±0.14 ng/mL, respectively; P<0.001). There was no significant correlation between plasma levels of PTX3 and BNP or CRP. Receiver operating characteristic (ROC) curves for screening PAH in patients with CTD revealed that PTX3 (area under the ROC curve 0.866) is superior to BNP. Using a PTX3 threshold of 2.85 ng/mL maximized true-positive and false-negative results (sensitivity 94.1{\%}, specificity 73.5{\%}). Conclusion: Plasma concentrations of PTX3 may be a better biomarker of PAH than BNP, especially in patients with CTD.",
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AU - Tamura, Yuichi

AU - Ono, Tomohiko

AU - Kuwana, Masataka

AU - Inoue, Kenji

AU - Takei, Makoto

AU - Yamamoto, Tsunehisa

AU - Kawakami, Takashi

AU - Fujita, Jun

AU - Kataoka, Masaharu

AU - Kimura, Kensuke

AU - Sano, Motoaki

AU - Daida, Hiroyuki

AU - Satoh, Toru

AU - Fukuda, Keiichi

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N2 - Background: Although inflammation is an important feature of pulmonary arterial hypertension (PAH), the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested whether plasma concentrations of human pentraxin 3 (PTX3), a local inflammatory marker, would be a useful biomarker for detecting PAH. Methods: Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH), and six with congenital heart disease), 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) were also determined. Results: Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P<0.001). Using a threshold level of 2.84 ng/mL, PTX3 yielded a sensitivity of 74.0% and a specificity of 84.0% for the detection of PAH. In CTD-PAH patients, mean PTX3 concentrations were significantly higher than in CTD patients without PAH (5.02±0.69 vs. 2.40±0.14 ng/mL, respectively; P<0.001). There was no significant correlation between plasma levels of PTX3 and BNP or CRP. Receiver operating characteristic (ROC) curves for screening PAH in patients with CTD revealed that PTX3 (area under the ROC curve 0.866) is superior to BNP. Using a PTX3 threshold of 2.85 ng/mL maximized true-positive and false-negative results (sensitivity 94.1%, specificity 73.5%). Conclusion: Plasma concentrations of PTX3 may be a better biomarker of PAH than BNP, especially in patients with CTD.

AB - Background: Although inflammation is an important feature of pulmonary arterial hypertension (PAH), the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested whether plasma concentrations of human pentraxin 3 (PTX3), a local inflammatory marker, would be a useful biomarker for detecting PAH. Methods: Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH), and six with congenital heart disease), 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) were also determined. Results: Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P<0.001). Using a threshold level of 2.84 ng/mL, PTX3 yielded a sensitivity of 74.0% and a specificity of 84.0% for the detection of PAH. In CTD-PAH patients, mean PTX3 concentrations were significantly higher than in CTD patients without PAH (5.02±0.69 vs. 2.40±0.14 ng/mL, respectively; P<0.001). There was no significant correlation between plasma levels of PTX3 and BNP or CRP. Receiver operating characteristic (ROC) curves for screening PAH in patients with CTD revealed that PTX3 (area under the ROC curve 0.866) is superior to BNP. Using a PTX3 threshold of 2.85 ng/mL maximized true-positive and false-negative results (sensitivity 94.1%, specificity 73.5%). Conclusion: Plasma concentrations of PTX3 may be a better biomarker of PAH than BNP, especially in patients with CTD.

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