Centre for Rheumatology Research, University College London, UK.
Expert Rev Clin Immunol. 2006 May;2(3):377-85. doi: 10.1586/1744666X.2.3.377.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disease characterized by the presence of autoantibodies, many of which are directed against antigens of nuclear origin. In the clinical setting, these antibodies are important in the management of patients with SLE, providing information about disease activity, subtype and prognosis. The clearance of apoptotic debris is defective in patients with SLE. This causes the inappropriate persistence of nuclear antigens and thus a breakdown in peripheral tolerance with ensuing autoantibody generation. Patients have a variety of self-directed antibodies, and it is increasingly clear that some, but not all, of these antibodies are directly pathogenic. This review discusses the current hypotheses regarding the features by which antibody pathogenicity may be determined and therefore predicted, as well as the mechanisms by which these autoantibodies cause tissue damage in SLE and in lupus nephritis in particular. Identifying these pathogenic antibodies may well hold the key to the development of new, targeted therapies.
系统性红斑狼疮（SLE）是一种多系统自身免疫性风湿病，其特征是存在自身抗体，其中许多自身抗体针对核源性抗原。在临床环境中，这些抗体在 SLE 患者的管理中非常重要，可提供有关疾病活动度、亚型和预后的信息。SLE 患者清除凋亡细胞碎片的能力存在缺陷。这导致核抗原的持续存在不当，从而破坏外周耐受，导致自身抗体产生。患者有多种自身指向性抗体，越来越清楚的是，这些抗体中的一些（但不是全部）具有直接致病性。这篇综述讨论了当前关于抗体致病性可能确定和预测的特征的假说，以及这些自身抗体在 SLE 中特别是狼疮肾炎中引起组织损伤的机制。鉴定这些致病性抗体可能是开发新的靶向治疗方法的关键。
