Center for Autoimmune Liver Diseases, Department of Medicine, IRCCS Istituto Clinico Humanitas, Rozzano, Italy.
J Autoimmun. 2012 May;38(2-3):J187-92. doi: 10.1016/j.jaut.2011.11.012. Epub 2011 Dec 16.
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.
X 染色体被认为包含人类基因组中最大数量的免疫相关基因。出于这个原因，X 染色体最近成为了极大的兴趣和关注的焦点，许多研究旨在了解 X 染色体上的基因在引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种日益严重的健康负担，累计影响高达 10%的普通人群。有趣的是，大多数 X 连锁原发性免疫缺陷症都伴有明显的自身免疫表现，这表明位于 X 染色体上的单个基因产物在免疫系统的启动、功能和稳态中起着关键作用。同样，特纳综合征患者观察到的大量自身免疫迹象也表明，X 连锁基因在自身免疫中起着独特而主要的作用。特纳综合征是一种由于缺少一条 X 染色体或存在主要 X 染色体缺失而导致的疾病，这种疾病表明 X 连锁基因在女性自身免疫性疾病中通过失活或复制具有基因剂量效应。最后，对于研究人员来说，未来几年的一个挑战将是从自身免疫疾病发展的角度来剖析大量 X 连锁 microRNAs 的作用。总之，X 染色体可能构成了易患自身免疫性疾病的共同特征，而不仅仅是解释这些疾病女性居多的原因。这篇综述将重点介绍 X 染色体改变的现有证据，并讨论其潜在的意义和局限性。
