Khan Wahid Ali, Habib Safia, Khan Wajid Ali, Alam Khursheed
Department of Biochemistry, J. N. Medical College, A. M. U., Aligarh, 202002, India.
Mol Cell Biochem. 2008 Aug;315(1-2):143-50. doi: 10.1007/s11010-008-9798-1. Epub 2008 Jun 10.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by circulating and tissue fixed autoantibodies reactive with self-antigens, including nucleic acid and other nuclear components. The pathways by which these autoantibodies act as a pathogenic factor remain elusive. Present study has investigated the role of estrogens in SLE etiopathogenesis. Estrogen-modified DNA [4-OHE(2)-Cu(II)-DNA] showed single- and double-strand breaks, hyperchromicity, decrease in Tm, and modification of bases. The 4-OHE(2)-Cu(II)-DNA exhibited increased binding with naturally occurring anti-DNA autoantibodies as compared to the unmodified native form (P < 0.001) as assessed by ELISA, quantitative precipitin titration, and gel retardation assay. The relative affinity of anti-DNA antibodies for modified and native DNA was in the order of 2.1 x 10(-7) M and 1.3 x 10(-6) M, respectively. The data suggested that DNA modified with 4-OHE(2) and Cu(II) may be one of the factors for the induction of circulating anti-DNA autoantibodies in SLE.
系统性红斑狼疮（SLE）是一种多系统自身免疫性疾病，其特征是循环和组织中存在与自身抗原（包括核酸和其他核成分）反应的自身抗体。这些自身抗体作为致病因素的作用途径仍不清楚。目前的研究调查了雌激素在SLE发病机制中的作用。雌激素修饰的DNA [4-羟基雌二醇（2）-铜（II）-DNA]显示出单链和双链断裂、增色效应、熔点降低以及碱基修饰。通过酶联免疫吸附测定（ELISA）、定量沉淀素滴定和凝胶阻滞试验评估，与未修饰的天然形式相比，4-羟基雌二醇（2）-铜（II）-DNA与天然存在的抗DNA自身抗体的结合增加（P < 0.001）。抗DNA抗体对修饰DNA和天然DNA的相对亲和力分别为2.1×10^(-7) M和1.3×10^(-6) M。数据表明，用4-羟基雌二醇（2）和铜（II）修饰的DNA可能是SLE中诱导循环抗DNA自身抗体的因素之一。
