Centre for Immunology and Allergy Research, Westmead Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
University of Queensland, Diamantina Institute, Translational Research Institute, The Queensland Brain Institute, University of Queensland, Australia.
J Autoimmun. 2017 Mar;78:57-69. doi: 10.1016/j.jaut.2016.12.006. Epub 2017 Jan 4.
Multiple Sclerosis (MS) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. The autoimmune and MS risk gene ZMIZ1 is underexpressed in blood in people with MS. We show that, from three independent sets of transcriptomic data, expression of ZMIZ1 is tightly correlated with that of hundreds of other genes. Further we show expression is partially heritable (heritability 0.26), relatively stable over time, predominantly in plasmacytoid dendritic cells and non-classical monocytes, and that levels of ZMIZ1 protein expression are reduced in MS. ZMIZ1 gene expression is increased in response to calcipotriol (1,25 Vitamin D3) (p < 0.0003) and associated with Epstein Barr Virus (EBV) EBNA-1 antibody titre (p < 0.004). MS therapies fingolimod and dimethyl fumarate altered blood ZMIZ1 gene expression compared to untreated MS. The phenotype indicates susceptibility to MS, and may correspond with clinical response and represent a novel clinical target.
多发性硬化症 (MS) 是一种神经系统疾病，部分由外周循环中的免疫细胞驱动，目前的成功治疗方法针对这些免疫细胞。自身免疫和 MS 风险基因 ZMIZ1 在 MS 患者的血液中表达不足。我们表明，从三组独立的转录组数据来看，ZMIZ1 的表达与数百个其他基因的表达密切相关。此外，我们还表明，其表达部分具有遗传性（遗传率 0.26），随时间相对稳定，主要存在于浆细胞样树突状细胞和非经典单核细胞中，并且 MS 患者的 ZMIZ1 蛋白表达水平降低。ZMIZ1 基因表达在钙泊三醇（1,25 维生素 D3）（p < 0.0003）和 Epstein Barr 病毒 (EBV) EBNA-1 抗体滴度（p < 0.004）的作用下增加。与未治疗的 MS 相比， fingolimod 和二甲基富马酸等 MS 疗法改变了血液 ZMIZ1 基因表达。这种表型表明易患 MS，可能与临床反应相对应，并代表一个新的临床目标。
