Endothelial biomarkers of systemic sclerosis-associated pulmonary hypertension. Arthritis care & research Lammi, M. R., Kolstad, K. D., Saketkoo, L. A., Khatri, A., Utz, P. J., Steen, V. D., Chung, L. 2023


Despite efforts at early detection, systemic sclerosis pulmonary hypertension (SSc-PH) patients present with advanced disease. We sought to determine whether endothelial biomarkers (asymmetric dimethylarginine [ADMA], soluble endoglin [sEng], and pentraxin-3 [PTX-3]) can determine SSc-PH risk or differentiate between SSc-PH subgroups.ADMA, sEng, and PTX-3 were measured by ELISA in four groups: 1) 18 healthy controls; 2) 74 SSc-PH patients; 3) 44 patients with high-risk for PH features; 4) 10 patients with low-risk for PH features. High-risk features included a diffusion capacity (DLCO) <55% with forced vital capacity (FVC) >70%, or an FVC/DLCO ratio of >1.6, or a right ventricular systolic pressure on echocardiogram =40mmHg. ADMA, sEng, and PTX-3 were compared between these four groups as well as stratified based on the three SSc-PH clinical classification groups (pulmonary arterial hypertension [PAH], left-heart disease [LHD], interstitial lung disease [ILD]).PTX-3 was significantly lower in SSc subjects at low risk for PH [median 27.0pg/mL [IQR 19.0, 47.3, p<0.003] than the other groups. The area under the receiving operator characteristic curve was 0.87 (95% CI 0.76-0.98, p=0.0002) to differentiate low-risk from high-risk for PH patients. PTX-3 was significantly lower in SSc-PH from LHD (57.5pg/mL [39.8, 79.0], p<0.01) compared to either SSc-PH from PAH (85.5pg/mL [56.3, 104.5]) or ILD (90.3pg/mL [74.9, 111.0]). Neither ADMA nor sEng differed between the four groups.Pentraxin-3 is a promising biomarker of PH risk status in SSc patients as well as a possible marker of pre-capillary pulmonary hypertension, which should be validated in an external cohort.

View details for DOI 10.1002/acr.25180

View details for PubMedID 37365746