Sexual dimorphism in SLE: above and beyond sex hormones.
Sexual dimorphism in SLE: above and beyond sex hormones.
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DOI：
10.1177/0961203318815768
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发表时间：
2019-01
期刊：
影响因子：
2.6
通讯作者：
Boumpas DT
中科院分区：
文献类型：
--
作者：
Christou EAA;Banos A;Kosmara D;Bertsias GK;Boumpas DT
系统性红斑狼疮(SLE)的特征是自身抗体的异常产生和男女之间的表型表达和疾病频率的性别二型性。这种惊人的女性优势最初主要归因于性激素。然而，最近的数据挑战了这种简单化的观点，并更多地指出了造成这种差异的遗传和表观遗传因素。更具体地说，几个与SLE相关的单核苷酸多态(SNPs)已被发现在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的信号传递以及与免疫系统相关的基因和miRNAs的表达失调来实现的。此外，遗传因素与表观遗传修饰(如DNA甲基化和组蛋白修饰)互换相关，从而揭示了一个高度复杂的负责机制网络。重要的是，在女性X染色体失活的表观遗传过程中的干扰以及罕见的X染色体异常会导致X连锁免疫相关基因和miRNAs的表达增加，这可能使女性容易患上SLE。通过肠道内雌激素的产生和雌激素反应免疫相关基因的调节，微生物区系失调也与性别二型性有关。SLE的性二型性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护理努力。
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.
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影响因子：
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作者：
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