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系统性红斑狼疮抗DNA自身抗体与儿茶酚雌激素修饰DNA的结合特性

Binding characteristics of SLE anti-DNA autoantibodies to Catecholestrogen-modified DNA.

作者信息

Khan W A

机构信息

Department of Biochemistry, Faculty of Medicine, J. N. Medical College, AMU, Aligarh, India.

出版信息

Scand J Immunol. 2006 Dec;64(6):677-83. doi: 10.1111/j.1365-3083.2006.01855.x.

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which anti-double-stranded DNA antibody is a classic autoantibody that characterizes SLE. A role for oestrogens in the pathogenesis of SLE has been suspected for many years but the exact patho-aetiology remains elusive. In this study, the binding of SLE autoantibodies with native and 4-OHE(2)-NO-modified plasmid DNA were assessed. Binding specificity of antibodies was analysed by direct binding and inhibition enzyme-linked immunosorbent assay, quantitative precipitin titration and gel retardation assay. Anti-DNA IgG from SLE sera, purified on Protein A-Agarose matrix, exhibited increased recognition of 4-OHE(2)-NO-DNA than native DNA (P < 0.001). Gel retardation assay further substantiated the enhanced recognition of modified DNA by anti-DNA autoantibodies. The affinity of anti-DNA antibodies for modified polymer was found to be high as calculated by using Langmuir plot. DNA modified by 4-OHE(2)-NO presents unique neo-epitopes that might be one of the factor in antigen-driven induction of SLE autoantibodies.

摘要

系统性红斑狼疮(SLE)是一种多系统自身免疫性疾病,其中抗双链DNA抗体是表征SLE的经典自身抗体。多年来一直怀疑雌激素在SLE发病机制中起作用,但确切的病理病因仍不清楚。在本研究中,评估了SLE自身抗体与天然和4-OHE(2)-NO修饰的质粒DNA的结合情况。通过直接结合和抑制酶联免疫吸附测定、定量沉淀素滴定和凝胶阻滞测定分析抗体的结合特异性。在蛋白A-琼脂糖基质上纯化的SLE血清中的抗DNA IgG对4-OHE(2)-NO-DNA的识别高于天然DNA(P < 0.001)。凝胶阻滞测定进一步证实了抗DNA自身抗体对修饰DNA的识别增强。通过使用朗缪尔图计算发现抗DNA抗体对修饰聚合物的亲和力很高。4-OHE(2)-NO修饰的DNA呈现独特的新表位,这可能是抗原驱动诱导SLE自身抗体的因素之一。

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