Cytokine Signatures Differentiate Systemic Sclerosis Patients at High Versus Low Risk for Pulmonary Arterial Hypertension

Kathleen D. Kolstad; Avani Khatri; Michele Donato; Sarah E. Chang; Shufeng Li; Virginia D. Steen; Paul J. Utz; Purvesh Khatri; Lorinda Chung


Arthritis Res Ther. 2022;24(39) 

In This Article


Systemic sclerosis (SSc) is an autoimmune rheumatic disease characterized by vasculopathy, immune system dysregulation, and fibrosis of the skin and internal organs. Pulmonary arterial hypertension (PAH) is a leading cause of death in patients with systemic sclerosis, affecting 8–12% of this patient population.[1,2] There is accumulating evidence that early PAH-specific therapy can improve survival and functional status in patients with SSc.[3] Early PAH screening and diagnosis has also been suggested to improve outcomes.[4,5] Right heart cathetherization (RHC) is the gold standard for the diagnosis of PAH. Given the invasive nature of this procedure, a variety of screening algorithms have been implemented to identify SSc patients at high risk for PAH and who warrant early referral to RHC. However, although many of the commonly used algorithms have high sensitivity (97–100%), they suffer from low specificity (26–55%) and marginal positive predictive value (60–67%).[6]

There has been increasing interest in identifying cytokines as biomarkers for disease severity and progression in patients with SSc and SSc-PAH. Furthermore, recognizing dysregulated cytokines has the potential to help understand the pathogenesis of disease and could identify therapeutic targets. Previous studies have detected changes in expression of individual cytokines involved in vascular injury and inflammation in patients with SSc-PAH compared to healthy controls and patients with SSc and no PAH. More specifically increases in inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand factor have been identified in patients with SSc-PAH.[7]

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 the 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.