Gene expression signatures for treatment response in systemic sclerosis

The goal of the current proposal is to assess whether gene expression analysis of skin using provides SSc biomarkers to predict disease course and clinical improvement during mycophenolate mophetil (MMF ) therapy. Preliminary experiments demonstrated that four out of four clinical responders belonged to the inflammatory intrinsic subset while the three non-responders belonged to the fibroproliferative or normal-like intrinsic subsets. In addition, a distinct 321-gene baseline expression signature that clearly distinguished clinical-responders from non-responders (baseline signature), and a 571-gene clinical response expression signature composed of genes whose expression changed during MMF treatment in responders only (response signature) were identified. These results suggest that gene expression in skin is a useful biomarker associated with MMF response. In this proposal, we will validate the gene expression subsets that we have delveloped by analyzing patients collected prospectively and using single sample predictor algorithms to identify the subsets to which they belong. Patients with SSc and matched healthy controls will be recruited from three large academic centers into a prospective, open-label, observational study. Assessments will include skin score, laboratory, heart and lung studies as clinically indicated. Appropriate patients will receive MMF for 1 year because that is the standard of care. Skin biopsies will be performed before treatment, and at 6 and 12 months during MMF treatment.