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Abstract Number: 1707

High Oxidative Stress in Fibrotic and Non-Fibrotic Skin of Patients with Systemic Sclerosis

Khalil I. Bourji1, Alain Meyer2,3, Emmanuel Chatelus2, Erika Pigatto1, François Singh3, Bernard Geny3, Leonardo Punzi1, Jacques-Eric Gottenberg2, Franco Cozzi1 and Jean Sibilia2, 1Division of Rheumatology, University Hospital of Padova, Padova, Italy, 2Division of Rheumatology, University Hospital of Strasbourg, Strasbourg, France, 3Physiology and Functional Explorations, University Hospital of Strasbourg, Strasbourg, France

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: biopsies, ROS, skin fibrosis and systemic sclerosis

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Session Information

Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics

Session Type: Abstract Submissions (ACR)

Background/Purpose

Systemic Sclerosis (SSc) is a chronic multisystemic connective tissue disease characterized by progressive fibrosis affecting skin and internal organs. Despite serious efforts to unveil pathogenic mechanisms of SSc, they are still unclear. High levels of Reactive Oxygen Species (ROS) in affected skin have been shown, but the role of oxidative stress remains controversial (1, 2, 3).  In this study we assess ROS levels in non-fibrotic (NS) and fibrotic (FS) skin of patients with SSc and we compare them with those obtained from healthy controls (CS).

Patients and Methods

We enrolled 9 SSc patients fulfilling the EULAR/ACR classification criteria (4) and 7 healthy controls.  Patients were 4 men and 5 women with mean age of  46±10 yrs.  Controls were matched by sex and age.  All patients were  affected by  diffuse cutaneous form of SSc and the ANA pattern  anti-Scl70. Mean disease duration was 7.5±5  yrs. Skin involvement was evaluated by modified Rodnan Skin Score (mRSS).  Skin samples (4mm punch biopsy) were taken from fibrotic skin (FS) and non-fibrotic skin (NS) of patients and from healthy controls (CS) as well. To detect ROS, specimens were analyzed immediately after sampling by electron paramagnetic resonance spectroscopy (5).

Results

ROS levels (expressed as median and range, unit of measurement was AU/mg) were 118.6×10³ (52.4 ×10³– 225.7×10³) in FS, 89.6×10³ (34.8 ×10³– 163.1×10³) in NS and 36.8×10³ (17×10³– 65.1×10³) in CS. ROS levels in Fibrotic (FS) and Non-fibrotic (NS) skin of SSc patients were significantly higher than in Healthy Control (CS) (p=0.002 and p=0.009, respectively).  Although ROS levels in FS were raised in comparison to NS, this difference was not statistically significant (p=0.24).  ROS levels of FS were correlated with DLCO (r= -0.59, p=0.09), VC (r= -0.75, p=0.02) and ESR (r=0.70, p=0.03). All other clinical and lab parameters showed no significant correlation.

Conclusion

Our results confirm the presence of high oxidative stress either in non-fibrotic skin (NS) or in fibrotic skin (FS) of SSc patients, but with higher tendency in the latter. Raised ROS levels in non-fibrotic skin (NS) of SSc patients might be a hint of early involvement in skin fibrogenesis.  However, a longitudinal prospective study is necessary for such proof.

 

References

1. Murrell DF. (1993). J Am Acad Dermatol.

2. Herrick AL et al. (2001). Clin Exp Rheumatol.

3. Matucci Cerinic M et al. (2002). Rheumatology.

4. Van den Hoogen F et al. (2013). Arthritis Rheum.

5. Zweier JL et al. (1987). Proc Natl Acad Sci USA.


Disclosure:

K. I. Bourji,
None;

A. Meyer,
None;

E. Chatelus,
None;

E. Pigatto,
None;

F. Singh,
None;

B. Geny,
None;

L. Punzi,
None;

J. E. Gottenberg,
None;

F. Cozzi,
None;

J. Sibilia,
None.

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