PT - JOURNAL ARTICLE AU - Catherine Simpson AU - Stephen Mathai AU - Todd Kolb AU - Paul Hassoun AU - Susan Aja AU - Aurelie Roux AU - David Graham AU - Rachel Damico TI - Metabolic profiling of pulmonary vascular phenotypes in systemic sclerosis AID - 10.1183/13993003.congress-2020.1524 DP - 2020 Sep 07 TA - European Respiratory Journal PG - 1524 VI - 56 IP - suppl 64 4099 - http://erj.ersjournals.com/content/56/suppl_64/1524.short 4100 - http://erj.ersjournals.com/content/56/suppl_64/1524.full SO - Eur Respir J2020 Sep 07; 56 AB - The molecular determinants of PAH risk and disease severity in systemic sclerosis (SSc) are poorly understood. We hypothesized that metabolic profiling of SSc serum would enable 1) discrimination of PAH, and 2) discovery of metabolic patterns associated with distinct pulmonary vascular phenotypes.Serum from 24 adult subjects with SSc (12 with and 12 without PAH) underwent mass spectrometry for targeted metabolomics. Metabolite associations with clinical variables were examined with standard statistical and bioinformatic approaches. 3 clusters of subjects with unique metabolic patterns were formed on the basis of metabolites alone, and clinical differences were compared across clusters.Metabolites of purine catabolism (e.g. hypoxanthine, raw p 0.027) and bile acid synthesis (e.g. glycocholate, raw p 0.006) differed in SSc with versus without PAH in significance analysis of metabolites. In SSc-PAH, metabolites discriminated subjects whose NYHA functional class improved with PAH therapy. A trend for increasing disease severity was observed across metabolite clusters, with more adverse hemodynamics, shorter 6 minute walk distance, and shorter survival time in cluster 1 compared to clusters 2 and 3 (Figure). Bile acid and caffeine metabolite concentrations contributed to cluster differences.Metabolites discriminate pulmonary vascular phenotypes in SSc. Unique metabolic patterns may be novel biomarkers of PAH risk and severity in SSc. Figure:FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1524.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).