Original Article
Subject Categories: Clinical Research
Journal of Investigative Dermatology (2004) 122, 594–601; doi:10.1111/j.0022-202X.2004.22333.x
Novel Autoantibody to Cu/Zn Superoxide Dismutase in Patients with Localized Scleroderma
Masaki Nagai, Minoru Hasegawa, Kazuhiko Takehara and Shinichi Sato
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
Correspondence: Dr Shinichi Sato, Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920–8641, Japan. Email: s-sato@med.kanazawa-u.ac.jp
Received 25 July 2003; Revised 18 September 2003; Accepted 24 September 2003; Published online 23 March 2004.
Abstract
Abnormal production of reactive oxygen species (ROS) induces tissue damage and superoxide dismutase (SOD) that converts superoxide radicals to hydrogen peroxide functions as defense against ROS. Cu/Zn SOD administration has been shown to be effective for various fibrotic conditions by inhibiting the fibrogenic effects of ROS. We hypothesized that autoimmune background in localized scleroderma induced anti-Cu/Zn SOD autoantibodies that inhibited SOD activity and thereby contributed to fibrosis by increasing ROS. ELISA using human purified Cu/Zn SOD revealed that IgG or IgM anti-Cu/Zn SOD Ab was detected in the serum of 89% of localized scleroderma patients, especially 100% of patients with generalized morphea, the severest form of localized scleroderma, but was positive only in the serum of less than 15% of patients with other autoimmune disorders, including systemic sclerosis, systemic lupus erythematosus, dermatomyositis, and autoimmune bullous disorders. The immunoblotting analysis confirmed the presence of IgG anti-Cu/Zn SOD Ab in sera from localized scleroderma patients. Remarkably, anti-Cu/Zn SOD autoantibody could inhibit Cu/Zn SOD enzymatic activity. Collectively, these results indicate that anti-Cu/Zn SOD Ab is a novel, major autoantibody in localized scleroderma, and also suggest that the autoantibody may play a role in the development of fibrosis by directly inhibiting SOD activity.
Keywords:
autoimmunity, fibrosis, reactive oxygen species
Abbreviations:
Ab, antibody; DM, dermatomyositis; PV/PF/BP, pemphigus vulgaris/pemphigus foliaceus/bullous pemphigoid; ROS, reactive oxygen species; SLE, systemic lupus erythematosus; SOD, superoxide dismutase; SSc, systemic sclerosis; ssDNA, single-stranded DNA; TGF-
, transforming growth factor-
; TIMP, tissue inhibitor of metalloproteinases
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