Human pentraxin 3 (PTX3) as a novel biomarker for the diagnosis of pulmonary arterial hypertension.

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

Clinical characteristics of patients with pulmonary arterial hypertension and healthy controls.

<p>Unless indicated otherwise, data are given as the mean ± SE.</p><p>PAH, pulmonary arterial hypertension; CAD, coronary artery diseases; CRP, C-reactive protein; BNP, B-type natriuretic peptide; NS, not significant.</p

Serum pentraxin 3 (PTX3) concentrations in 50 patients with pulmonary arterial hypertension (PAH) and 100 healthy controls, and their correlation with serum concentrations of other biomarkers.

<p>A: Comparison of PTX3 concentrations in PAH patients and healthy controls. Mean plasma PTX3 concentrations were 4.40±0.37 and 1.94±0.09 ng/mL in the controls and PAH patients, respectively. B: Distribution of log-transformed PTX3 concentrations in PAH patients and healthy controls. C: Log-transformed PTX3 concentrations were significantly higher in patients with PAH than in healthy controls (1.34±0.07 vs. 0.55±0.05 log ng/mL, respectively; <i>P</i><0.001). D, E: There was no correlation between plasma concentrations of PTX3 and either B-type natriuretic peptide (BNP; <i>r</i> = 0.33, <i>P</i> = 0.02) or C-reactive protein (CRP; <i>r</i> = 0.21, <i>P</i> = 0.14) in PAH patients.</p

Receiver operating characteristic (ROC) curves for pentraxin 3 (PTX3).

<p>The area under the ROC curve was 0.866 (95% confidence interval 0.805–0.928). The star indicates the threshold concentration of 2.84 ng/mL PTX3 that maximized true-positive and false-negative results (sensitivity 74.0%, specificity 84.0%).</p

Receiver operating characteristic (ROC) curves for pentraxin 3 (PTX3) and other biomarkers in patients with connective tissue disease (CTD).

<p>The areas under the ROC curve (AUC_ROC) for PTX3 was 0.866 (95% confidence interval (CI) 0.757–0.974). The star indicates the threshold concentration of 2.85 ng/mL PTX3 that maximized true-positive and false-negative results (sensitivity 94.1%, specificity 73.5%). The AUC_ROC for C-reactive protein (CRP) was 0.518 (95% CI 0.333–0.704), whereas that for B-type natriuretic peptide (BNP) was 0.670 (95% CI 0.497–0.842).</p