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Differential expression of hepatocyte growth factor in patients with systemic sclerosis-associated pulmonary arterial hypertension

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Article Type: BRIEF REPORT

Article Subject: Epidemiology and Diagnostic Methods

DOI:10.5301/jsrd.5000245

Authors

Yon K. Sung, Roham T. Zamanian, Catriona A. Wagner, William Robinson, Virginia Steen, Lorinda Chung

Abstract

IntroductionNon-invasive biomarkers are needed to identify pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) patients who may benefit from early intervention. We sought to identify novel cytokines that differentiate patients with incident SSc-PAH from those at high risk for PAH.

MethodsThe Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) Registry is a multicenter registry of SSc patients at high risk for PAH (at-risk) or with incident right-heart catheterization-confirmed PAH (definite PAH). Serum from 10 at-risk and 9 definite PAH patients were profiled with Bio-PlexTM bead arrays for 48 cytokines and chemokines. We also evaluated the longitudinal change in cytokine profiles from 3 at-risk patients who subsequently developed definite PAH.

ResultsClinical features of at-risk versus definite PAH patients were not significantly different except for right-ventricular systolic pressure on echocardiogram (34 ± 7 vs. 45 ± 8 mmHg, p = 0.006), left atrial diameter (2.9 ± 0.5 vs. 3.7 ± 0.4 cm, p = 0.02), 6-minute walk distance (508 ± 115 vs. 393 ± 70 m, p = 0.02), mean pulmonary artery pressure (18 ± 4 vs. 32 ± 6 mmHg, p = 0.01), and pulmonary vascular resistance (111 ± 48 vs. 272 ± 109 dyn/s/cm5, p = 0.009). Serum cytokine profiling identified hepatocyte growth factor (HGF) as the only cytokine significantly different between the at-risk and definite PAH groups (225.8 ± 55.0 vs. 361.6 ± 164.5 pg/mL, q<0.1%). Profiling of longitudinal samples of at-risk to definite PAH patients did not identify any significant changes in HGF or other cytokines over time.

ConclusionsDefinite PAH patients expressed higher levels of HGF than at-risk patients. Further studies are needed to clarify the utility of HGF as a predictive biomarker for SSc-PAH.

Article History

Disclosures

Financial support: The PHAROS registry was initially funded by Actelion, the Scleroderma Foundation, and the Sibley Foundation, with ongoing funding from Gilead. However, the sponsors did not participate in the writing, study design, collection, analysis, or interpretation of the data.
Conflict of interest: Dr. Zamanian receives research funding from Actelion, United Therapeutics, and Eiger Pharmaceuticals. He has been a consultant to Actelion, Bayer, United Therapeutics, and Selten Pharmaceuticals. Dr. Steen has served on an Advisory Board for Gilead Science, Bristol-Myers Squibb, and Bayer, and has been a consultant for United Therapeutics, Reata, and Cytori. She has received research funding from Gilead Science, United Therapeutics, and CSL Behring. Dr. Chung receives funding support from the Scleroderma Research Foundation, the Scleroderma Foundation, and the Scleroderma Clinical Trials Consortium. She has served on the Advisory Board for Gilead and Actelion, and the Data Safety Monitoring Board for Reata and Cytori. She has received research funding from United Therapeutics. Dr. Sung, Ms. Wagner, and Dr. Robinson declare no conflicts of interest.

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