Wen Ying-Hao, Lin Wei-Tzu, Wang Wei-Ting, Chen Ding-Ping
Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
J Clin Med. 2021 Feb 20;10(4):871. doi: 10.3390/jcm10040871.
Transfusion reactions are mainly induced by the interaction of an antigen and antibody. However, transfusion reactions still occur with the implementing of crossmatching and usage of pre-storage leukoreduced blood products. The roles of CD28 and CTLA4 gene polymorphisms in transfusion reaction have been shown, and subjects with certain single nucleotide polymorphisms (SNPs) of the CD28 or CTLA4 gene had a significantly higher risk of transfusion reactions. In total, 40 patients with transfusion reactions after receiving pre-storage leukoreduced blood products were enrolled in this study. We focused on the SNPs located in the CD28 promoter region (rs1879877, rs3181096, rs3181097, and rs3181098) to find out the significant SNP. A luciferase reporter assay was used to investigate the expression level of protein affected by promoter SNP variation. We found that the polymorphism of rs3181097 was associated with transfusion reactions ( = 0.003 in additive model and = 0.015 in dominant model). Consequently, we investigated the biological function in the CD28 promoter polymorphisms (rs1879877 G > T, rs3181096 C > T, rs3181097 G > A, and rs3181098 G > A) by using dual-spectral luciferase reporter assay. The results showed that the ex-pression level of CD28 was decreased under the effect of rs3181097 with A-allele. This suggested that rs3181097 may regulate immune response through decreasing CD28 protein expression and then lead to development of transfusion reactions.
输血反应主要由抗原与抗体的相互作用引起。然而，即使实施了交叉配血并使用了储存前白细胞滤除的血液制品，输血反应仍会发生。CD28和CTLA4基因多态性在输血反应中的作用已得到证实，具有CD28或CTLA4基因某些单核苷酸多态性（SNP）的受试者发生输血反应的风险显著更高。本研究共纳入40例接受储存前白细胞滤除血液制品后发生输血反应的患者。我们聚焦于位于CD28启动子区域的SNP（rs1879877、rs3181096、rs3181097和rs3181098）以找出显著的SNP。采用荧光素酶报告基因检测法研究启动子SNP变异对蛋白质表达水平的影响。我们发现rs3181097的多态性与输血反应相关（加性模型中P = 0.003，显性模型中P = 0.015）。因此，我们通过双荧光素酶报告基因检测法研究了CD28启动子多态性（rs1879877 G>T、rs3181096 C>T、rs3181097 G>A和rs3181098 G>A）的生物学功能。结果显示，在rs3181097的A等位基因作用下，CD28的表达水平降低。这表明rs3181097可能通过降低CD28蛋白表达来调节免疫反应，进而导致输血反应的发生。
