Poole Brian D, Scofield R Hal, Harley John B, James Judith A
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma, OK 73104, USA.
Autoimmunity. 2006 Feb;39(1):63-70. doi: 10.1080/08916930500484849.
Systemic lupus erythematosus (SLE or lupus) is a complex disease with a multifactoral etiology, with genetic, hormonal, and environmental influences. Molecular mimicry as a result of viral infection may contribute to the development of lupus. The pattern of autoantibody development in lupus is consistent with initiation through molecular mimicry, as the initial autoantigenic epitopes that have been observed are limited and cross-reactive with viral proteins. Autoantibody specificity may then later diversify to other autoantigens through B-cell epitope spreading. Epstein-Barr virus (EBV) is an excellent candidate to be involved in molecular mimicry in lupus. EBV infection has been associated with lupus through serological and DNA studies. Infection with EBV results in the production of the viral protein Epstein-Barr virus nuclear antigen-1 (EBNA-1), antibodies against which cross-react with lupus-associated autoantigens, including Ro, Sm B/B', and Sm D1, in lupus patients. The immune response against EBV, and EBNA-1 in particular, differs among lupus patients and healthy controls, with controls maintaining a limited humoral response and failing to produce long-standing cross-reactive antibodies. We hypothesize that the humoral immune response to EBNA-1 in susceptible individuals leads to the generation of cross-reactive antibodies. Through the process of epitope spreading, these cross-reactive antibodies target additional, non-cross reactive autoepitopes, spread to additional autoantigens, and become pathogenic, leading eventually to clinical lupus. This paper reviews some of the current literature supporting roles for EBV exposure and epitope spreading in SLE.
系统性红斑狼疮（SLE或狼疮）是一种病因多因素的复杂疾病，受遗传、激素和环境影响。病毒感染导致的分子模拟可能促使狼疮的发生。狼疮中自身抗体的产生模式与通过分子模拟引发的情况一致，因为已观察到的初始自身抗原表位有限且与病毒蛋白存在交叉反应。随后，自身抗体特异性可能通过B细胞表位扩展而多样化至其他自身抗原。爱泼斯坦 - 巴尔病毒（EBV）是参与狼疮分子模拟的极佳候选者。通过血清学和DNA研究，EBV感染已与狼疮相关联。EBV感染会导致病毒蛋白爱泼斯坦 - 巴尔病毒核抗原1（EBNA - 1）的产生，狼疮患者体内针对该抗原的抗体与包括Ro、Sm B/B'和Sm D1在内的狼疮相关自身抗原发生交叉反应。狼疮患者和健康对照对EBV，尤其是EBNA - 1的免疫反应有所不同，对照维持有限的体液反应且无法产生长期存在的交叉反应抗体。我们推测，易感个体对EBNA - 1的体液免疫反应会导致交叉反应抗体的产生。通过表位扩展过程，这些交叉反应抗体靶向其他非交叉反应性自身表位，扩散至其他自身抗原，并变得具有致病性，最终导致临床狼疮。本文综述了一些支持EBV暴露和表位扩展在SLE中作用的当前文献。
