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Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
 
Arthritis Res Ther. 2012; 14(3): R145.
Published online Jun 14, 2012. doi:  10.1186/ar3879
PMCID: PMC3446529
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
Dimitrios Daoussis,corresponding author#1 Athanassios C Tsamandas,#2 Stamatis-Nick C Liossis,#1 Ioannis Antonopoulos,1 Elli Karatza,2 Georgios Yiannopoulos,1 and Andrew P Andonopoulos1
1Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Patras, Rion, 26504, Greece
2Department of Pathology, Patras University Hospital, University of Patras Medical School, Patras, Rion, 26504, Greece
corresponding authorCorresponding author.
#Contributed equally.
Dimitrios Daoussis: jimdaoussis/at/hotmail.com; Athanassios C Tsamandas: tsa/at/otenet.gr; Stamatis-Nick C Liossis: sliossis/at/hotmail.com; Ioannis Antonopoulos: iantonopoulos/at/hotmail.co.uk; Elli Karatza: ekaratza/at/otenet.gr; Georgios Yiannopoulos: ggmser/at/otenet.gr; Andrew P Andonopoulos: andandon/at/upatras.gr
Received November 23, 2010; Revised May 7, 2012; Accepted June 14, 2012.
Abstract
Introduction
Recently, several studies assessing the clinical efficacy of rituximab (RTX) in systemic sclerosis (SSc) have reported encouraging results. We aimed at exploring whether RTX exerts its beneficial effects on fibrosis through attenuation of platelet-derived growth factor receptor (PDGFR) pathway activation.
Methods
We immunohistochemically assessed skin biopsies obtained from eight patients with SSc prior to and 6 months following RTX treatment, three control SSc patients (at the same time points) and three healthy subjects. We assessed the expression of platelet-derived growth factor, PDGFR and phosphorylated (activated) PDGFR.
Results
We found a strong correlation of PDGFRα and PDGFRβ expression on spindle-like cells and collagen deposition in SSc biopsies (r = 0.97 and r = 0.96 for PDGFRα and PDGFRβ, respectively; P < 0.0001 for both), indicating a strong link between PDGFR expression and fibrosis. Expression of PDGFRα and PDGFRβ in the papillary dermis significantly decreased following RTX administration (mean ± standard error of the mean at baseline vs. 6 months, respectively: PDGFRα, 42.05 ± 5.03 vs. 26.85 ± 3.00, P = 0.004; and PDGFRβ, 37.14 ± 4.94 vs. 24.01 ± 3.27, P = 0.012). Similarly, expression of phosphorylated PDGFRα and PDGFRβ in the papillary dermis significantly decreased following RTX administration (P = 0.006 and P = 0.013 for phospho-PDGFRα and phospho-PDGFRβ, respectively). No changes in platelet-derived growth factor tissue expression or serum levels were found following RTX treatment.
Conclusion
RTX may favorably affect skin fibrosis through attenuation of PDGFR expression and activation, a finding that supports a disease-modifying role of RTX in SSc. Large-scale, multicenter studies are needed to further explore the efficacy of RTX in SSc.
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