The following is a summary of “Metabolomic Profiles Differentiate Scleroderma-PAH From Idiopathic PAH and Correspond With Worsened Functional Capacity,” published in the January 2023 issue of Chest by Alotaibi, et al.
Pulmonary arterial hypertension due to systemic sclerosis (SSc-PAH) has a worse prognosis and less success with treatment than idiopathic PAH (IPAH). Discrepancies in these measures may be due to differences in the metabolic determinants of disease. Patients with idiopathic pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension due to SSc were included in the study by providing plasma biosamples. For external validation, they also included a second cohort of 100 patients with scleroderma who did not have PH and 44 patients with scleroderma who did have PH.
Over 700 bioactive lipid metabolites were measured in plasma samples from separate discovery and validation cohorts using liquid chromatography/high-resolution mass spectrometry-based methods. These metabolites represented a variety of vasoactive and immune-inflammatory pathways. Regression analyses were conducted to determine which metabolites were associated with disease severity in SSc-PAH versus IPAH and showed levels that were different between the two.
About 5 metabolites were identified from hundreds of bioactive lipid molecules in circulation that were diagnostic of SSc-PAH and IPAH and associated with disease severity markers. Patients with SSc-PAH had higher levels of fatty acid metabolites, such as lignoceric acid and nervonic acid, eicosanoids/oxylipins, and sex hormone metabolites, compared to those with IPAH. An unfavorable bioactive metabolic profile, which may explain the poor and limited response to therapy in SSc-PAH patients, is characterized by several factors. These data provide insights into the metabolic heterogeneity underlying differences between PAH subgroups.
Source: sciencedirect.com/science/article/abs/pii/S0012369222037060
