Project description:Skin gene expression signatures, including intrinsic subset, are associated with skin score/MRSS improvement during mycophenolate mofetil (MMF) treatment.
Project description:Skin gene expression signatures, including intrinsic subset, are associated with improvement during Mycophenolate mofetil (MMF) treatment.
Project description:Background: Only a subset of patients with systemic sclerosis (SSc) demonstrate improvement in modified Rodnan skin score (mRSS) during mycophenolate mofetil (MMF) treatment. Here we investigated the molecular and cellular effects in skin associated with MMF therapy in subjects who demonstrated or lacked clinical improvement. Methods: Clinical and skin gene expression data were obtained genome-wide from baseline and longitudinal (6-, 12-, 24-, and 36-mo) biopsies in 33 MMF-treated subjects with SSc. Clinical improvement was defined as mRSS reduction ≥ 25%. An inflammatory signature score was calculated for each patient sample using single-sample gene set enrichment analysis (ssGSEA). Cell type specific changes during treatment were characterized. Results: Eleven subjects with SSc completed at least 24 months of MMF therapy and were termed ‘completers’. Two distinct gene expression patterns were observed that corresponded to MMF treatment status. Three subjects showed attenuation of the inflammatory signature by 24 months, paralleling reductions in activated dendritic cells. MMF cessation at 24 months resulted in an inflammatory signature rebound paralleling mRSS increase. Three subjects that remained on MMF showed persistent inflammatory signature reductions with decreasing or stable mRSS. The remaining six completers either did not fulfill minimum mRSS (n=5), and/or lacked a baseline inflammatory signature (n=4). Conclusions: An elevated inflammatory skin gene expression signature is associated with clinical improvement during MMF therapy. Inflammation returned upon MMF discontinuation with concomitant mRSS increase. These data summarize MMF’s molecular effects in skin and support MMF therapy for longer than 24 months in patients who demonstrate clinical response.
Project description:Skin gene expression signatures, including intrinsic subset, are associated with skin score/MRSS improvement during mycophenolate mofetil (MMF) treatment. Gene expression and intrinsic subset assignment were measured in SSc patients amd controls at baseline, and from biopsies of MMF-treated patients.
Project description:Skin gene expression signatures, including intrinsic subset, are associated with improvement during Mycophenolate mofetil (MMF) treatment. Longitudinal SSc patient biopsies and controls were integrated into 83 sample dataset totaling 165 arrays for gene expression and analysis
Project description:Systemic sclerosis is associated with skin fibrosis thought mediated by TGFb. This open label clinical trial examines the effect of TGFb inhibition on skin gene expression. Patients 1-9 received two doses 1 mg/kg dose of fresolimumab at baseline and 3 weeks; patients 10-19 received a single 5 mg/kg dose Patients with diffuse cutaneous systemic sclerosis within 2 years of first raynauds had skin biopsies before treatment and the 3-4 weeks, 7 weeks and 24 weeks after treatment with fresolimumab
Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation and fibrosis of the skin and internal organs. We sought to assess the clinical and molecular effects associated with response to intravenous abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).
