Abstract
IntroductionSignificant pulmonary vascular disease is a leading cause of death in patients with scleroderma, and early detection and early medical intervention are important, as they may delay disease progression and improve survival and quality of life. Although several biomarkers have been proposed, there remains a need to define a reliable biomarker of early pulmonary vascular disease and subsequent development of pulmonary hypertension (PH). The purpose of this study was to define potential biomarkers for clinically significant pulmonary vascular disease in patients with scleroderma.MethodsThe circulating growth factors basic fibroblast growth factor, placental growth factor (PlGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor, and soluble VEGF receptor 1 (sFlt-1), as well as cytokines (interleukin [IL]-1β IL-2, IL-4, IL-5, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor-α, and interferon-γ), were quantified in patients with scleroderma with PH (n = 37) or without PH (n = 40). In non-parametric unadjusted analyses, we examined associations of growth factor and cytokine levels with PH. In a subset of each group, a second set of earlier samples, drawn 3.0±1.6 years earlier, were assessed to determine the changes over time.ResultssFlt-1 (p = 0.02) and PlGF (p = 0.02) were higher in the PH than in the non-PH group. sFlt-1 (ρ = 0.3245; p = 0.01) positively correlated with right ventricular systolic pressure. Both PlGF (p = 0.03) and sFlt-1 (p = 0.04) positively correlated with the ratio of forced vital capacity to diffusing capacity for carbon monoxide (DLCO), and both inversely correlated with DLCO (p = 0.01). Both PlGF and sFlt-1 levels were stable over time in the control population.ConclusionsOur study demonstrated clear associations between regulators of angiogenesis (sFlt-1 and PlGF) and measures of PH in scleroderma and that these growth factors are potential biomarkers for PH in patients with scleroderma. Larger longitudinal studies are required for validation of our results.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0712-4) contains supplementary material, which is available to authorized users.
Highlights
Significant pulmonary vascular disease is a leading cause of death in patients with scleroderma, and early detection and early medical intervention are important, as they may delay disease progression and improve survival and quality of life
Additional subgroups included the following groups according to World Health Organization (WHO) pulmonary hypertension (PH) guidelines: (1) Pulmonary arterial hypertension (PAH) with mean pulmonary arterial pressure (mPAP) ≥25 mmHg, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, and forced vital capacity (FVC) ≥70 %; (2) PH and significant restrictive ventilatory defects (RVD); and (3) pulmonary venous hypertension (PVH)
We found that IL-8 (p = 0.02), Tumor necrosis factor alpha (TNF-α) (p = 0.02), Soluble fms-like tyrosine kinase-1 (sFlt-1) (p = 0.02), and Hepatocyte growth factor (HGF) (p = 0.01) were associated with age and that there were no significant associations between biomarkers and skin score or disease duration
Summary
Significant pulmonary vascular disease is a leading cause of death in patients with scleroderma, and early detection and early medical intervention are important, as they may delay disease progression and improve survival and quality of life. Several biomarkers have been proposed, there remains a need to define a reliable biomarker of early pulmonary vascular disease and subsequent development of pulmonary hypertension (PH). Pulmonary hypertension (PH) is a common complication of scleroderma, with an estimated 8–12 % of patients developing pulmonary arterial disease [8, 19]. Several biomarkers have been proposed [1, 2, 6], there remains a need to define a reliable biomarker of early pulmonary vascular disease and provide. McMahan et al Arthritis Research & Therapy (2015) 17:201 insight into disease mechanisms. The goal of this pilot study was to investigate potentially relevant biomarkers associated with the presence of PH that could be tested in a longitudinal cohort study
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