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Updated: May 21, 2026
Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
B-cell depletion therapy in patients with diffuse systemic sclerosis associates with a significant decrease in PDGFR
Dimitrios Daoussis1, Athanassios C Tsamandas, Stamatis-Nick C Liossis
1Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Patras, Rion, 26504, Greece. jimdaoussis@hotmail.com
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.
Insights
Rituximab (RTX) treatment may reduce skin fibrosis in systemic sclerosis (SSc) by decreasing platelet-derived growth factor receptor (PDGFR) activation. This suggests RTX has a disease-modifying role in SSc.
Area of Science:
- Immunology
- Dermatology
- Rheumatology
Background:
- Systemic sclerosis (SSc) is a fibrotic disease.
- Rituximab (RTX) shows promise in treating SSc.
- The mechanism of RTX's effect on fibrosis is being investigated.
Purpose of the Study:
- To explore if RTX reduces fibrosis in SSc by affecting the platelet-derived growth factor receptor (PDGFR) pathway.
- To assess changes in PDGFR expression and activation after RTX treatment in SSc patients.
Main Methods:
- Skin biopsies from SSc patients before and after RTX treatment were analyzed.
- Immunohistochemistry was used to measure PDGFR, phosphorylated PDGFR, and platelet-derived growth factor.
- Expression levels were compared between treated patients, control SSc patients, and healthy subjects.
Main Results:
- PDGFRα and PDGFRβ expression strongly correlated with fibrosis in SSc skin.
- RTX treatment significantly decreased PDGFRα and PDGFRβ expression in the papillary dermis.
- Phosphorylated PDGFRα and PDGFRβ levels also significantly decreased after RTX administration.
Conclusions:
- RTX may improve skin fibrosis in SSc by reducing PDGFR pathway activation.
- These findings support a disease-modifying potential for RTX in SSc.
- Larger studies are needed to confirm RTX efficacy in SSc.
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