局限性硬皮病中的抗DNA拓扑异构酶IIα自身抗体

Anti-DNA topoisomerase IIalpha autoantibodies in localized scleroderma.

作者信息

Hayakawa Ikuko, Hasegawa Minoru, Takehara Kazuhiko, Sato Shinichi

机构信息

Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

出版信息

Arthritis Rheum. 2004 Jan;50(1):227-32. doi: 10.1002/art.11432.

DOI:10.1002/art.11432

PMID:14730620

Abstract

OBJECTIVE

To determine the prevalence and clinical correlation of anti-DNA topoisomerase IIalpha (anti-topo IIalpha) antibody in patients with localized scleroderma.

METHODS

Anti-topo IIalpha antibodies or anti-DNA topoisomerase I (topo I) antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Inhibition of topo IIalpha enzymatic activity by the antibodies was evaluated by decatenation assays using kinetoplast DNA as a substrate.

RESULTS

IgG or IgM anti-topo IIalpha antibody was detected in 76% (35 of 46) of patients with localized scleroderma, and in 85% (11 of 13) of patients with generalized morphea, the severest form of localized scleroderma. This prevalence of the antibody in patients with localized scleroderma was much higher than that found in patients with systemic sclerosis (SSc) (5 of 37 [14%]), systemic lupus erythematosus (2 of 26 [8%]), dermatomyositis (2 of 20 [10%]), and in healthy controls (3 of 42 [7%]). Immunoblotting confirmed the presence of IgG anti-topo IIalpha antibody in sera from patients with localized scleroderma and showed no cross-reactivity of anti-topo IIalpha antibody with topo I. Anti-topo I antibody was not detected by ELISA in any sera from patients with localized scleroderma. In addition, anti-topo I antibody from SSc patients did not cross-react with topo IIalpha. The presence of anti-topo IIalpha antibody was associated with a greater total number of sclerotic lesions and number of plaque lesions in patients with localized scleroderma. Furthermore, anti-topo IIalpha antibody was able to inhibit topo IIalpha enzymatic activity.

CONCLUSION

The results of the present study indicate that anti-topo IIalpha is a major autoantibody in localized scleroderma, and is distinct from anti-topo I antibody in SSc.

摘要

目的

确定局限性硬皮病患者中抗DNA拓扑异构酶IIα（抗拓扑异构酶IIα）抗体的患病率及其临床相关性。

方法

采用酶联免疫吸附测定（ELISA）和免疫印迹法检测抗拓扑异构酶IIα抗体或抗DNA拓扑异构酶I（拓扑异构酶I）抗体。以动质体DNA为底物，通过解连环测定评估抗体对拓扑异构酶IIα酶活性的抑制作用。

结果

在局限性硬皮病患者中，76%（46例中的35例）检测到IgG或IgM抗拓扑异构酶IIα抗体，在局限性硬皮病最严重的泛发性硬斑病患者中，该比例为85%（13例中的11例）。局限性硬皮病患者中该抗体的患病率远高于系统性硬化症（SSc）患者（37例中的5例[14%]）、系统性红斑狼疮患者（26例中的2例[8%]）、皮肌炎患者（20例中的2例[10%]）以及健康对照者（42例中的3例[7%]）。免疫印迹证实局限性硬皮病患者血清中存在IgG抗拓扑异构酶IIα抗体，且抗拓扑异构酶IIα抗体与拓扑异构酶I无交叉反应。ELISA在局限性硬皮病患者的任何血清中均未检测到抗拓扑异构酶I抗体。此外，SSc患者的抗拓扑异构酶I抗体与拓扑异构酶IIα无交叉反应。局限性硬皮病患者中抗拓扑异构酶IIα抗体的存在与硬化性病变总数及斑块状病变数量增多有关。此外，抗拓扑异构酶IIα抗体能够抑制拓扑异构酶IIα的酶活性。