Ye Yi, Berendine Van Zyl, Hellmich Charlotte, Gillespie Kathleen M
Diabetes and Metabolism, School of Clinical Sciences, University of Bristol UK.
Int J Mol Epidemiol Genet. 2010 Sep 11;1(4):350-7.
While the world of genetics has been dominated over the last decade by technological advances allowing the identification of common variants underlying the major complex diseases, it is increasingly clear that other genetic mechanisms are also involved in genetic susceptibility and resistance to disease. One understudied contender is microchimerism (maternal and foetal), resulting from bi-directional transfer of cells across the placental barrier in pregnancy. Data from several diseases suggest that elevated levels of microchimerism are associated with autoimmunity. Theories differ however on the role of these cells in the disease process. Some suggest that they increase genetic susceptibility while others suggest that these cells are effectors of the immune response, or that they represent the target of the immune response while another proposes that elevated levels in disease are caused by ongoing repair of damaged tissue. Intriguingly these semi allogeneic cells are tolerated in healthy individuals, albeit at a lower level than in disease scenarios and recent studies in cancer suggest that foetal microchimeric cells may provide surveillance and repair. Many questions remain to be answered about this new avenue of genetics. It is likely that as technology advances our understanding of, and ability to manipulate these cells for therapeutic gain, will push forward new frontiers in medicine.
在过去十年中,遗传学领域一直由技术进步主导,这些技术进步使得人们能够识别导致主要复杂疾病的常见变异。然而,越来越明显的是,其他遗传机制也参与了对疾病的遗传易感性和抵抗力。一个研究较少的因素是微嵌合体(母体和胎儿的),它是由孕期细胞通过胎盘屏障的双向转移产生的。来自几种疾病的数据表明,微嵌合体水平升高与自身免疫有关。然而,关于这些细胞在疾病过程中的作用,理论存在分歧。一些人认为它们会增加遗传易感性,而另一些人则认为这些细胞是免疫反应的效应器,或者它们是免疫反应的靶点,还有人提出疾病中水平升高是由受损组织的持续修复引起的。有趣的是,这些半同种异体细胞在健康个体中是可以耐受的,尽管水平低于疾病状态,最近的癌症研究表明,胎儿微嵌合细胞可能提供监测和修复功能。关于这个新的遗传学领域,仍有许多问题有待解答。随着技术的进步,我们对这些细胞的理解以及为了治疗获益而操纵它们的能力,很可能会推动医学的新前沿。