Cytokine signatures differentiate systemic sclerosis patients at high versus low risk for pulmonary arterial hypertension [65-plex]

Pulmonary arterial hypertension (PAH) affects approximately 10% of patients with systemic sclerosis (SSc) and is a leading cause of death. We sought to identify serum cytokine signatures that risk stratify SSc patients for this potentially fatal complication. In the current study we aimed to characterize specific cytokine signatures that differentiate patients with incident SSc-PAH, patients at high risk for SSc-PAH, patients at low risk for SSc-PAH, and healthy controls. We anticipate these data will assist with early identification of patients at high risk for or with incident SSc-PAH. Additionally, we expect this study will identify cytokines that may be involved in the pathogenesis of SSc-PAH and could serve as therapeutic targets. Subjects at high-risk for PAH and with incident PAH based on right heart catheterization (RHC) were enrolled in the multi-center prospective registry, Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS). Low-risk SSc patients were enrolled at Stanford and had normal pulmonary function test and echocardiogram parameters. Serum was available from 71 high-risk patients, 81 incident PAH patients, 10 low-risk patients, and 20 healthy controls (HC). Custom 14 and 65-plex arrays were used for cytokine analysis. Cytokine expression was compared between patient groups by principal component analysis and Tukey’s test result. A multiple hypotheses corrected p-value <0.05 was considered significant. Submitter note: Two samples (U013 and U132) in the 65-plex are identical, but not because they are duplicates. This is because of the background correction after which all values are zero for these two samples.