Serum Adipokines as Predictors of Organ Involvement and Progression in Scleroderma

Systemic sclerosis is characterized by diffuse fibrosis and vasculopathy. SSc has the potential to affect nearly every organ system and continues to carry the highest mortality rate of the rheumatic diseases [1]. Establishing means by which to predict disease progression is crucial to improving management of systemic sclerosis and its complications. There is an urgent need to discover and validate biomarkers in SSc to serve as easily quantifiable surrogate markers for disease activity and clinical end points. Work from our group demonstrates that altered adipose tissue metabolism is a hallmark of SSc [2]. Furthermore we’ve shown adipokines, specific peptides secreted by adipose tissue, are dysregulated in SSc, and could be utilized as potential mechanistic and predictive biomarkers [3]. To date the focus on adipokines in SSc has remained primarily on adiponectin, leptin and resistin. However two recent meta-analyses evaluating the circulating levels of these adipokines both detected a significant difference only in adiponectin levels in SSc patients with no significant change in either leptin or resistin levels in SSc vs. controls [4, 5]. Our group has identified two entirely novel adipokines, CTRP9 and adipsin, which have strong published and unpublished data supporting their association with pulmonary and vascular complications of SSc respectively [6, 7]. Yet to date, the utility of these and other adipokines remains unclear given limitations in associative and cross sectional data. Our objective is to fulfill the unmet need for prognostic biomarkers that can predict both disease progression and development in SSc.