Christou E A A, Banos A, Kosmara D, Bertsias G K, Boumpas D T
1 Laboratory of Inflammation and Autoimmunity, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
2 Department of Rheumatology, Clinical Immunology and Allergy, University of Crete School of Medicine, Heraklion, Greece.
Lupus. 2019 Jan;28(1):3-10. doi: 10.1177/0961203318815768. Epub 2018 Dec 1.
Systemic lupus erythematosus (SLE) is characterized by aberrant production of auto-antibodies and a sexual dimorphism both in the phenotypic expression and frequency of the disease between males and females. The striking female predominance was initially attributed primarily to sex hormones. However, recent data challenge this simplistic view and point more towards genetic and epigenetic factors accounting for this difference. More specifically, several SLE-associated single-nucleotide polymorphisms (SNPs) have been found to play an important role in the gender predilection in SLE. Their effect is mediated through their involvement in sex-hormone and immune system signalling and dysregulation of the expression of genes and miRNAs pertinent to the immune system. Additionally, the genetic factors are interchangeably associated with epigenetic modifications such as DNA methylation and histone modification, thus revealing a highly complex network of responsible mechanisms. Of importance, disturbance in the epigenetic process of X chromosome inactivation in females as well as in rare X chromosome abnormalities leads to increased expression of X-linked immune-related genes and miRNAs, which might predispose females to SLE. Microbiota dysbiosis has also been implicated in the sexual dimorphism by the production of oestrogens within the gut and the regulation of oestrogen-responsive immune-related genes. Sexual dimorphism in SLE is an area of active research, and elucidation of its molecular basis may facilitate ongoing efforts towards personalized care.
系统性红斑狼疮（SLE）的特征是自身抗体产生异常，并且在疾病的表型表达和男女发病率方面存在性别差异。女性明显占主导地位最初主要归因于性激素。然而，最近的数据对这种简单化观点提出了挑战，更多地指向遗传和表观遗传因素是造成这种差异的原因。更具体地说，已发现几种与SLE相关的单核苷酸多态性（SNP）在SLE的性别偏好中起重要作用。它们的作用是通过参与性激素和免疫系统信号传导以及与免疫系统相关的基因和微小RNA（miRNA）表达失调来介导的。此外，遗传因素与DNA甲基化和组蛋白修饰等表观遗传修饰相互关联，从而揭示了一个高度复杂的相关机制网络。重要的是，女性X染色体失活的表观遗传过程紊乱以及罕见的X染色体异常会导致X连锁免疫相关基因和miRNA的表达增加，这可能使女性易患SLE。肠道微生物群失调也通过肠道内雌激素的产生和雌激素反应性免疫相关基因的调节与性别差异有关。SLE中的性别差异是一个活跃的研究领域，阐明其分子基础可能有助于正在进行的个性化医疗努力。
