目前异基因造血干细胞移植（allo-HSCT）后Epstein-Barr病毒（EBV）相关疾病已经成为移植后的重要并发症与死亡原因之一，但不同地域人群发病率差异较大。本研究拟①通过研究HLA多态性和细胞因子基因单核苷酸多态性（SNPs）与allo-HSCT后EBV感染/再激活、EBV相关疾病的关联，探讨基因多态性对EBV相关疾病的影响，揭示不同地域人群发病率差异的原因；②检测不同基因型个体EBV特异性的细胞毒性T细胞（EBV-CTL）的水平和效应能力，探讨基因多态性影响EBV相关疾病的机制；③检测细胞因子基因启动子区域SNPs对转录能力的影响和外显子区域SNPs对蛋白表达水平的影响，探讨细胞因子基因SNPs参与EBV相关疾病的机制；④采用具有不同基因型的EBV血清学阳性供者的外周血单个核细胞诱导严重免疫缺陷小鼠发生EBV相关肿瘤，验证不同基因多态性对EBV相关疾病发生的影响。

Epstein-Barr virus (EBV)-associated diseases have become a major complication and cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT).The incidence of EBV-associated diseases varies greatly in different areas. In this study, the association between gene polymorphisms (including HLA polymorphisms and cytokine gene single nucleotide polymorphisms [SNPs]) and EBV infection as well as EBV-associated diseases will be evaluated in order to explore the effect of polymorphisms on EBV-associated diseases and provide plausible explanation of the different incidence in different areas. To provide a possible mechanism to explain the link between gene polymorphisms and EBV-associated diseases, EBV-specific cytotoxic T lymphocytes (EBV-CTL) response restricted through different alleles will be studies. Transcriptional activity of different cytokine gene SNPs in promoter will be studied using luciferase reporter gene systems and electrophoretic mobility shift assays, and protein levels of different cytokine gene SNPs in exon will be tested using western-blotting. Human peripheral blood leukocytes derived from donors with different alleles will be injected to severe-combined immunodeficient mice to test the hypothesis that gene polymorphisms associates with the development of EBV-associated disease.