Table_6_Zinc metabolism and its role in immunity status in subjects with trisomy 21: chromosomal dosage effect.docx

IntroductionTrisomy 21 (T21), which causes Down syndrome (DS), is the most common chromosomal aneuploidy in humankind and includes different clinical comorbidities, among which the alteration of the immune system has a heavy impact on patient’s lives. A molecule with an important role in immune response is zinc and it is known that its concentration is significantly lower in children with T21. Different hypotheses were made about this metabolic alteration and one of the reasons might be the overexpression of superoxide dismutase 1 (SOD1) gene, as zinc is part of the SOD1 active enzymatic center.
MethodsThe aim of our work is to explore if there is a linear correlation between zinc level and immune cell levels measured in a total of 217 blood samples from subjects with T21. Furthermore, transcriptome map analyses were performed using Transcriptome Mapper (TRAM) software to investigate whether a difference in gene expression is detectable between subjects with T21 and euploid control group in tissues and cells involved in the immune response such as lymphoblastoid cells, thymus and white blood cells.
ResultsOur results have confirmed the literature data stating that the blood zinc level in subjects with T21 is lower compared to the general population; in addition, we report that the T21/control zinc concentration ratio is 2:3, consistent with a chromosomal dosage effect due to the presence of three copies of chromosome 21. The transcriptome map analyses showed an alteration of some gene’s expression which might explain low levels of zinc in the blood.
DiscussionOur data suggest that zinc level is not associated with the levels of immunity cells or proteins analyzed themselves and rather the main role of this ion might be played in altering immune cell function.

引言
21三体综合征（Trisomy 21, T21）即唐氏综合征（Down syndrome, DS），是人类最常见的染色体非整倍体疾病，伴随多种临床合并症，其中免疫系统异常对患者生活质量影响显著。锌是在免疫应答中发挥重要作用的分子，已有研究证实，21三体综合征患儿体内的锌浓度显著降低。针对这一代谢异常已有多种假说，其中一种可能的原因是超氧化物歧化酶1（superoxide dismutase 1, SOD1）基因的过表达——因为锌是SOD1活性酶促中心的组成成分。
方法
本研究旨在探究21三体综合征患者的217份全血样本中，锌水平与免疫细胞水平是否存在线性相关关系。此外，本研究使用转录组图谱分析（Transcriptome Mapper, TRAM）软件进行转录组图谱分析，以比较21三体综合征患者与整倍体对照组在免疫应答相关组织及细胞（如淋巴母细胞、胸腺及白细胞）中的基因表达差异。
结果
本研究结果证实了已有文献结论：21三体综合征患者的血锌水平低于普通人群；此外我们发现，21三体综合征组与对照组的锌浓度比值为2:3，这与21号染色体存在3个拷贝所导致的染色体剂量效应相符。转录组图谱分析显示，部分基因的表达异常可解释患者体内血锌水平偏低的现象。
讨论
本研究数据表明，锌水平与本次分析所检测的免疫细胞或蛋白水平本身并无关联，反而锌离子可能主要通过改变免疫细胞功能发挥作用。