The X chromosome and immune associated genes
The X chromosome and immune associated genes
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DOI：
10.1016/j.jaut.2011.11.012
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发表时间：
2012-05-01
影响因子：
12.8
通讯作者：
Invernizzi, Pietro
中科院分区：
文献类型：
--
作者：
Bianchi, Ilaria;Lleo, Ana;Invernizzi, Pietro
已知的X染色体包含了整个人类基因组中数量最多的免疫相关基因。正因为如此，X染色体最近成为人们极感兴趣和关注的对象，许多研究旨在了解X染色体上的基因在触发和维持自身免疫攻击中的作用。自身免疫性疾病确实是一个日益严重的健康负担，累计影响总人口的10%。有趣的是，大多数X连锁的初级免疫缺陷都具有显著的自身免疫表现，从而说明了位于X染色体上的单基因产物在免疫系统的启动、功能和动态平衡中发挥的关键作用。同样，在Turner综合征患者中观察到过多的自身免疫性斑点，这是一种由于缺乏一条X染色体或存在主要X染色体缺失而引起的疾病，表明X连锁基因在自身免疫中发挥着独特的主要作用。关于X染色体基因剂量通过失活或复制在患有自身免疫性疾病的女性中的作用，例如通过具有单个X染色体(即X单体)的更高比率的循环细胞，已经有几个报告。最后，研究人员在未来几年面临的一个挑战将是从自身免疫性疾病发展的角度剖析大量X-连锁microRNAs的作用。综上所述，X染色体很可能构成了自身免疫性疾病易感性的共同特征，而不是解释这些疾病的女性优势。这篇综述将集中于现有的关于X染色体改变的证据，并讨论它们的潜在意义和局限性。(C)2011爱思唯尔有限公司。保留所有权利。
The X chromosome is known to contain the largest number of immune-related genes of the whole human genome. For this reason, X chromosome has recently become subject of great interest and attention and numerous studies have been aimed at understanding the role of genes on the X chromosome in triggering and maintaining the autoimmune aggression. Autoimmune diseases are indeed a growing heath burden affecting cumulatively up to 10% of the general population. It is intriguing that most X-linked primary immune deficiencies carry significant autoimmune manifestations, thus illustrating the critical role played by products of single gene located on the X chromosome in the onset, function and homeostasis of the immune system. Again, the plethora of autoimmune stigmata observed in patients with Turner syndrome, a disease due to the lack of one X chromosome or the presence of major X chromosome deletions, indicate that X-linked genes play a unique and major role in autoimmunity. There have been several reports on a role of X chromosome gene dosage through inactivation or duplication in women with autoimmune diseases, for example through a higher rate of circulating cells with a single X chromosome (i.e. with X monosomy). Finally, a challenge for researchers in the coming years will be to dissect the role for the large number of X-linked microRNAs from the perspective of autoimmune disease development. Taken together, X chromosome might well constitute the common trait of the susceptibility to autoimmune diseases, other than to explain the female preponderance of these conditions. This review will focus on the available evidence on X chromosome changes and discuss their potential implications and limitations. (C) 2011 Elsevier Ltd. All rights reserved.