Autoantibody against peroxiredoxin I, an antioxidant enzyme,
in patients with systemic sclerosis: possible association with
Y. Iwata1,3, F. Ogawa1, K. Komura1, E. Muroi1, T. Hara1, K. Shimizu1, M. Hasegawa2, M. Fujimoto2,
Y. Tomita3and S. Sato1
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 (n¼70) and healthy controls (n¼23) 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
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.
KEYWORDS: Systemic sclerosis, Oxidative stress, Peroxiredoxin, Pulmonary fibrosis, Autoantibody.
Systemic sclerosis (SSc) is a connective tissue disease that is
characterized by fibrosis and vascular changes in the skin
and other internal organs with autoimmune background .
Although the pathogenesis of SSc remains unknown, it has been
proposed that oxidative stress may play an important role in the
development of SSc . Ischaemia and reperfusion injury
following Raynaud’s phenomenon can generate reactive oxygen
species that may result in vascular endothelial damage [3, 4].
Reactive oxygen species are also released from skin fibroblasts of
SSc patients in vitro  and have been shown to stimulate
fibroblast proliferation, which may result in fibrosis [6, 7].
Furthermore, enhanced oxidative stress in SSc has been demon-
strated, since 8-isoprostane, a reliable biomarker of oxidative
stress, increases in urine [7, 8], bronchoalveolar lavage , and
serum samples  in patients with SSc and serum 8-isoprostane
levels correlate with the disease severity of SSc .
Exposure to reactive oxygen species from a variety of sources
has led organisms to develop a series of defence mechanism .
One of the important defence mechanisms against oxidative
stress is defence by antioxidant enzymes, including peroxiredoxin
(Prx), which is a recently discovered and characterized family
of thiol-specific antioxidant enzyme [12–14]. Prxs have peroxidase
hydrogen peroxide, peroxynitrate, and various organic hydro-
peroxides [15–17]. Prxs, which are present in a large variety of
organisms, are produced at high levels in cells [15, 16, 18]. Six Prx
isoforms (Prxs I–VI) have been identified  and Prx I is the most
abundant and ubiquitously distributed member of the mammalian
Prxs . Recently, Karasawa et al.  have shown that 33% of
patients with systemic autoimmune diseases, including systemic
lupus erythematosus, primary vasculitis syndrome and rheuma-
toid arthritis, possess autoantibodies to Prx I. However, the
prevalence and clinical correlation of anti-Prx I antibody (Ab) in
patients with SSc and whether anti-Prx I Ab was able to
inhibit the enzymatic activity of Prx I remained unknown in
Autoantibody production is one of the central features in SSc,
since more than 90% of patients have antinuclear Abs .
Although it remains controversial whether SSc-specific auto-
antibodies, such as anti-topoisomerase I, anticentromere and
anti-RNA-polymerase Abs, directly contribute to the clinical
manifestations of SSc, there may be possibilities that several
autoantobodies play a pathogenetic role [1, 21]. Therefore, we
hypothesized that anti-Prx I Ab could also be detected in patients
with SSc and contribute to enhanced oxidative stress by inhibiting
Prx I enzymatic activity, leading to tissue damage of SSc. To test
this possibility, the presence or levels of anti-Prx I Ab, its clinical
correlation and its functional significance were investigated in
the current study.
Serum samples were obtained from 70 Japanese patients with SSc
(61 women and 9 men). All patients fulfilled the criteria proposed
by the American College of Rheumatology . Patients were
grouped according to the classification system proposed by
1Department of Dermatology, Nagasaki University Graduate School of Biomedical
Sciences, Nagasaki,2Department of Dermatology, Kanazawa University Graduate
School of Medical Science, Kanazawa and3Department of Dermatology, Nagoya
University Graduate School of Medicine, Nagoya, Japan.
Submitted 23 October 2006; revised version accepted 3 January 2007.
Correspondence to: S. Sato, Department of Dermatology, Nagasaki University
Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501,
Japan. E-mail: email@example.com
Advance Access publication 19 February 2007
? The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: firstname.lastname@example.org
by guest on December 21, 2015
In conclusion, our study suggests that IgG anti-Prx I autoanti-
body is related to enhanced oxidative stress and is a useful
serological marker for the disease severity of SSc. In addition,
this autoantibody may contribute to the development of SSc by
inhibiting Prx I enzymatic activity.
The authors have declared no conflicts of interest.
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Rheumatology key messages
? IgG anti-Prx I antoantibody is associated with the disease severity
? Anti-Prx I antibody may enhance the oxidative stress by inhibiting
Prx I enzymatic activity.
Anti-Prx I autoantibody in SSc795
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