Open Access Research article

High serum sCD163/sTWEAK ratio is associated with lower risk of digital ulcers but more severe skin disease in patients with systemic sclerosis

Otylia Kowal-Bielecka1*, Marek Bielecki2, Serena Guiducci3, Beata Trzcinska-Butkiewicz4, Małgorzata Michalska-Jakubus5, Marco Matucci-Cerinic3, Marek Brzosko4, Dorota Krasowska5, Lech Chyczewski6 and Krzysztof Kowal7

Author Affiliations

1 Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland

2 Department of Orthopedics and Traumatology, Medical University of Bialystok, Bialystok, Poland

3 Department of BioMedicine, Division of Rheumatology AOUC, & Department of Medicine, Denothe Center, University of Florence, Florence, Italy

4 Department of Rheumatology and Internal Medicine, Medical University of Szczecin, Szczecin, Poland

5 Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland

6 Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland

7 Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland

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Arthritis Research & Therapy 2013, 15:R69  doi:10.1186/ar4246

Published: 24 June 2013

Abstract

Introduction

Systemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. CD163 is a scavenger receptor which affects inflammatory response and may contribute to connective tissue remodelling. It has recently been demonstrated that CD163 can bind and neutralize the TNF-like weak inducer of apoptosis (TWEAK), a multifunctional cytokine which regulates inflammation, angiogenesis and tissue remodelling. We aimed to investigate the relationships between serum levels of soluble CD163 (sCD163) and soluble TWEAK (sTWEAK) in relation to disease manifestations in SSc patients.

Methods

This study included 89 patients with SSc who had not received immunosuppressive drugs or steroids for at least 6 months and 48 age- and sex-matched healthy controls (HC) from four European centres. Serum concentrations of sTWEAK and sCD163 were measured using commercially available ELISA kits.

Results

The mean serum concentrations of sTWEAK were comparable between SSc patients (mean +/- SD: 270 +/- 171 pg/mL) and HC (294 +/- 147pg/mL, P >0.05). Concentration of sCD163 and sCD163/sTWEAK ratio were significantly greater in SSc patients (984 +/- 420 ng/mL and 4837 +/- 3103, respectively) as compared to HC (823 +/- 331 ng/mL and 3115 +/- 1346 respectively, P <0.05 for both). High sCD163 levels and a high sCD163/sTWEAK ratio (defined as > mean +2SD of HC) were both associated with a lower risk of digital ulcers in SSc patients (OR, 95%CI: 0.09; 0.01, 0.71, and 0.17; 0.06, 0.51, respectively). Accordingly, patients without digital ulcers had a significantly higher sCD163 concentration and sCD163/sTWEAK ratio as compared to SSc patients with digital ulcers (P <0.01 for both) and HC (P <0.05 for both). A high sCD163/sTWEAK ratio, but not high sCD163 levels, was associated with greater skin involvement.

Conclusions

The results of our study indicate that CD163-TWEAK interactions might play a role in the pathogenesis of SSc and that CD163 may protect against the development of digital ulcers in SSc. Further studies are required to reveal whether targeting of the CD163-TWEAK pathway might be a potential strategy for treating vascular disease and/or skin fibrosis in SSc.