Table 1.
Summary of potential protein biomarkers in SSc-PAH.
| Protein | Comparison Groups | Number of Patients | Outcome | Correlations in SSc-PAH | Reference |
|---|---|---|---|---|---|
| NT-proBNP | SSc-PAH vs. SSc SSc-PAH vs. SSc SSc-PAH vs. IPAH |
109 329 98 |
Significantly higher in SSc-PAH vs. SSc. Sens 55.9%, Spec 95.1%. Correlated with invasive hemodynamics NT-proBNP superior to BNP for detection of PAH in SSc Significantly higher in SSc-PAH, correlated with hemodynamics and predicted survival in SSc-PAH group. |
mPAP (r = 0.62; p < 0.0001) PVR (r = 0.81; p < 0.0001) CI (r = −0.58; p < 0.01) PVR (r = 0.54; p < 0.01) |
(12) (13) (14) |
| Endoglin | SSc-PAH vs. SSc vs. HV | 60 | Serum levels significantly higher in SSc-PAH than control | (15) | |
| sFLT-1 | SSc-PAH vs. SSc | 77 | Plasma levels significantly higher in SSc-PAH and correlate with RVSP and inversely with DLCO. Possible predictor of PH progression. | RVSP (r = 0.32; p = 0.01) DLCO (−0.29; p = 0.01) |
(16) |
| PlGF | SSc-PAH vs. SSc | 77 | Plasma levels significantly higher in SSc-PAH. Correlates with severity of Raynaud's phenomenon and inversely with DLCO. | DLCO (r = −0.031; p = 0.01) | (16) |
| VEGF-A | SSC-PAH vs. SSc vs. HV | 53 | Serum levels significantly higher in SSc-PAH than either SSc or HV. Levels correlate with echocardiographic sPAP, dyspnoea score and DLCO. | sPAP (r = 0.58; p < 0.01) DLCO (r = −0.47; p < 0.01) | (17) |
| GDF-15 | SSc-PAH vs. SSc | 54 | Plasma levels significantly higher in SSc-PAH, correlate with echocardiographic RVSP and circulating NT-proBNP. Discriminates between PH and non-PH. | RVSP (r = 0.56; p < 0.001) | (18) |
| RELM-ß | SSc-PAH vs. IPAH vs. HV | 26 | Tissue concentrations significantly higher in SSc-PAH than in IPAH or HV. | (19) | |
| sThrombomodulin | SSc-PAH vs. SSc vs. HV | 92 | Significantly higher plasma levels in SSc-PAH compared to either SSc or HV. | (20) |
NT-proBNP, N-terminal pro-brain type natriuretic protein; sFLT-1, soluble vascular endothelial growth factor receptor 1; PlGF, placenta growth factor; VEGF-A, vascular endothelial growth factor A; GDF-15, growth differentiation factor-15; RELM-ß, resistin like molecule-ß; sThrombomodulin, soluble thrombomodulin; SSc-PAH, systemic sclerosis related pulmonary arterial hypertension; SSc, systemic sclerosis; IPAH, idiopathic pulmonary arterial hypertension; HV, healthy volunteer; Sens, sensitivity; PH, pulmonary hypertension; Spec, specificity; mPAP, mean pulmonary artery pressure; PVR, pulmonary vascular resistance; CI, cardiac index; RVSP, right ventricular systolic pressure; DLCO, diffusing capacity for carbon monoxide; sPAP, systolic pulmonary artery pressure; EC, endothelial cells.