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Rheumatology Advance Access originally published online on February 19, 2007
Rheumatology 2007 46(5):790-795; doi:10.1093/rheumatology/kem010
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis: possible association with oxidative stress

Y. Iwata1,3, F. Ogawa1, K. Komura1, E. Muroi1, T. Hara1, K. Shimizu1, M. Hasegawa2, M. Fujimoto2, Y. Tomita3 and S. Sato1

1Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 2Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa and 3Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Correspondence to: S. Sato, Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. E-mail: s-sato{at}nagasaki-u.ac.jp


  Abstract

Objectives. To determine the prevalence and clinical correlation of autoantibody to peroxiredoxin (Prx) I, an antioxidant enzyme, in patients with systemic sclerosis (SSc).

Methods. Serum samples from SSc patients (n = 70) and healthy controls (n = 23) were examined by ELISA using human recombinant Prx I. The presence of anti-Prx I antibody was further evaluated by immunoblotting analysis. To determine the functional relevance of anti-Prx I antibody in vivo, we assessed whether anti-Prx I antibody was able to inhibit Prx I enzymatic activity using yeast thioredoxin reductase system.

Results. IgG anti-Prx I antibody levels in SSc patients were significantly higher than healthy controls and this autoantibody was detected in 33% of SSc patients. The presence of IgG anti-Prx I antibody was associated with longer disease duration, more frequent presence of pulmonary fibrosis, heart involvement, and anti-topoisomerase I antibody and increased levels of serum immunoglobulin and erythrocyte sedimentation rates. IgG anti-Prx I antibody levels also correlated positively with renal vascular damage and negatively with pulmonary function tests. Furthermore, anti-Prx I antibody levels correlated positively with serum levels of 8-isoprostane, a marker of oxidative stress. Immunoblotting analysis confirmed the presence of anti-Prx I antibody. Remarkably, Prx I enzymatic activity was inhibited by IgG isolated from SSc sera containing IgG anti-Prx I antibody.

Conclusions. These results suggest that elevated IgG anti-Prx I autoantibody is associated with the disease severity of SSc and that anti-PrxI antibody may enhance the oxidative stress by inhibiting Prx I enzymatic activity.

KEY WORDS: Systemic sclerosis, Oxidative stress, Peroxiredoxin, Pulmonary fibrosis, Autoantibody

Submitted 23 October 2006; revised version accepted 3 January 2007.
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