B cell depletion therapy in patients with diffuse systemic sclerosis associates with a significant decrease in PDGFR expression and activation in spindle-like cells in the skin Full Text
Arthritis Research & Therapy,
Daoussis D et al. – Rituximab (RTX) may favorably affect skin fibrosis through attenuation of PDGFR expression and activation, a finding that supports a disease modifying role of RTX in systemic sclerosis (SSc). Larger scale, multicenter studies are needed to further explore the efficacy of RTX in SSc.Methods
- The authors immunohistochemically assessed skin biopsies obtained from 8 patients with SSc prior to and 6 months following RTX treatment, 3 control SSc patients (at the same time points) and 3 healthy subjects.
- They assessed the expression of platelet derived growth factor (PDGF), PDGF receptor (PDGFR) and phosphorylated (activated) PDGFR.
- They found a strong correlation of PDGFRalpha and PDGFRbeta expression on spindle–like cells and collagen deposition in SSc biopsies (r=0.97 and r=0.96, for PDGFRalpha and PDGFRbeta, respectively, p<0.0001 for both) indicating a strong link between PDGFR expression and fibrosis.
- Expression of PDGFRalpha and PDGFRbeta in the papillary dermis significantly decreased following RTX administration (mean +/– SEM for PDGFRalpha: 42.05 +/– 5.03 vs 26.85 +/– 3.00, at baseline vs 6 months respectively, p=0.004 and for PDGFRbeta: 37.14 +/– 4.94 vs 24.01 +/– 3.27 at baseline vs 6 months respectively, p=0.012).
- Similarly, expression of phosphorylated PDGFRalpha and PDGFRbeta in the papillary dermis significantly decreased following RTX administration (p=0.006 and p=0.013 for phospho–PDGFRalpha and phospho–PDGFRbeta respectively).
- No changes in PDGF tissue expression or serum levels were found following RTX treatment.