Zhou Cheng, Jin Xiaoli, Tang Jie, Fei Jiaqian, Gu Chunxia, Chen Xi
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Cell Physiol Biochem. 2015;35(1):83-91. doi: 10.1159/000369677. Epub 2015 Jan 2.
CD40 is an important costimulatory molecule in both cellular and humoral immune responses, involved in the pathogenic processes of chronic inflammatory diseases. Few studies were performed on the association of CD40 single nucleotide polymorphism (SNP) with chronic hepatitis B virus (HBV) infection. In this study, we studied whether the CD40-1C/T polymorphism had any effect on the progression of chronic HBV infection in Chinese population.
CD40 -1C/T polymorphism in the 5'-untranslated region was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 453 chronic HBV carriers, who were divided into asymptomatic HBV carriers (ASC), moderate chronic hepatitis B group (MCHB) and severe chronic hepatitis B group (SCHB). 202 healthy individuals in the same region were enrolled in this study as the controls. The CD40 expression on B lymphocytes was detected by flow cytometry. The concentrations of soluble CD40 (sCD40) in sera were assayed by a commercial ELISA kit.
Our results showed the frequencies of TT genotype and T allele of CD40-1C/T polymorphism were higher significantly in ASC than those in controls (P< 0.05), while this result was not found in either MCHB or SCHB. On the surface of B lymphocytes, the CD40 expression levels in the individuals with TT genotype were significantly lower than those with CC and CT genotypes in either ASC group or healthy controls (P<0.001). The sCD40 levels in the sera of ASC, MCHB and SCHB groups were significantly higher than the controls (P<0.001).
The CD40 -1C/T polymorphism may contribute to the susceptibility of asymptomatic HBV carriers through its effect on cell-surface CD40 expression, which indicated CD40 signaling was involved in immune tolerance of chronic HBV infection.
CD40是细胞免疫和体液免疫应答中一种重要的共刺激分子，参与慢性炎症性疾病的发病过程。关于CD40单核苷酸多态性（SNP）与慢性乙型肝炎病毒（HBV）感染相关性的研究较少。在本研究中，我们探讨了CD40-1C/T多态性对中国人群慢性HBV感染进展的影响。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术分析453例慢性HBV携带者5'-非翻译区的CD40 -1C/T多态性，这些患者被分为无症状HBV携带者（ASC）、中度慢性乙型肝炎组（MCHB）和重度慢性乙型肝炎组（SCHB）。选取同一地区202名健康个体作为对照。采用流式细胞术检测B淋巴细胞表面CD40的表达。用商品化的ELISA试剂盒检测血清中可溶性CD40（sCD40）的浓度。
我们的研究结果显示，ASC组中CD40-1C/T多态性的TT基因型和T等位基因频率显著高于对照组（P<0.05），而MCHB组和SCHB组未发现此结果。在B淋巴细胞表面，无论是ASC组还是健康对照组中，TT基因型个体的CD40表达水平均显著低于CC和CT基因型个体（P<0.001）。ASC组、MCHB组和SCHB组血清中的sCD40水平均显著高于对照组（P<0.001）。
CD40 -1C/T多态性可能通过影响细胞表面CD40的表达，导致无症状HBV携带者易感性增加，这表明CD40信号通路参与了慢性HBV感染的免疫耐受。
