A Proteome derived longitudinal pharmacodynamic biomarker for diffuse systemic sclerosis skin.

In this study we systematically investigated alterations in the serum proteome of patients with diffuse cutaneous systemic sclerosis (dcSSc), and identified differentially expressed proteins that correlated with disease severity. Our goal was to identify a combination of serum proteins that would provide a biological measure for the extent of skin disease and that could be combined into a longitudinal pharmacodynamic biomarker. 16% of the sera proteins analyzed by SOMAscan aptamer technology, from two cohorts of dcSSc patients were identified as differentially regulated between dcSSc and controls, and correlated with the MRSS. This dataset revealed TNFα, IFNγ, TGFβ and IL-13 as potential upstream regulators of the serum protein patterns in dcSSc sera. By ELISA two analytes (ST2 and Spondin-1) best described longitudinal change in MRSS, using linear mixed models. This model was then validated in three independent cohorts. In this study we discovered a large array of proteins, not previously associated with SSc that provide insights into pathogenesis and potential targets for therapeutic intervention. Furthermore, we show that two of these proteins can be combined to form a robust longitudinal biomarker that might be utilized in clinical trials to assess changes in dcSSc skin disease over time.