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目的探讨家系内慢性乙型肝炎病毒感染与人类白细胞抗原-Ⅱ(HLA-Ⅱ)类基因多态性的关系及可能的原因。方法采用聚合酶链反应序列特异性引物(PCR/SSP)对(37个)慢性乙型肝炎病毒感染家系内成员(慢性HBV感染组121人,HBsAg阴性组76人)的人类白细胞抗原(HLA)DQA1和DQB1等位基因多态性进行分析;并从外周血中分离单个核细胞,在培养基中诱导培养为树突状细胞(DC),采用混合淋巴细胞反应检测DC刺激淋巴细胞增殖的能力。结果 HLA-DQA1 0501和DQB1 0301,DQB1 0201在慢性乙型肝炎病毒(HBV)感染组的等位基因频率明显高于HBsAg阴性组;HLA-DQB1 0402和DQB1 0604等位基因频率明显低于HBsAg阴性组;慢性HBV感染组DC刺激淋巴细胞增殖的刺激指数(SI)与HBsAg阴性组比较明显降低(P<0.01);HLA-DQA1 0501、DQB1 0301阳性组DC刺激淋巴细胞增殖指数明显低于阴性组;HLA-DQB1 0402、DQB1 0604阳性组淋巴细胞增殖指数明显高于阴性组。结论家系内HBV慢性感染与HLA-DQA1和DQB1的基因多态性相关,HLA-Ⅱ类基因可通过影响DC刺激淋巴细胞增殖能力发挥免疫调查作用,可能与HBV感染慢性化有关。
Objective To investigate the relationship between the chronic hepatitis B virus (HBV) infection and the human leucocyte antigen-Ⅱ (HLA-Ⅱ) gene polymorphism in pedigrees and possible causes. Methods Human leukocyte antigen (HLA) was detected in 37 (37) chronic hepatitis B virus infected individuals (121 in chronic HBV infection group and 76 in HBsAg negative group) by polymerase chain reaction sequence specific primers (PCR / SSP) DQA1 and DQB1 alleles were analyzed. Mononuclear cells were isolated from peripheral blood and cultured in the medium to dendritic cells (DCs). The mixed lymphocyte reaction was used to detect the ability of DCs to stimulate the proliferation of lymphocytes . Results The frequencies of alleles of HLA-DQA1 0501, DQB1 0301 and DQB1 0201 in patients with chronic hepatitis B virus infection were significantly higher than those in HBsAg-negative patients. The frequencies of HLA-DQB1 0402 and DQB1 0604 alleles were significantly lower than those of HBsAg-negative Group; the stimulation index (SI) of DCs stimulating lymphocyte proliferation in chronic HBV infection group was significantly lower than that in HBsAg negative group (P <0.01); the proliferation index of DCs stimulated by DCs in HLA-DQA1 0501 and DQB1 0301 positive groups was significantly lower than that in negative group ; HLA-DQB1 0402, DQB1 0604-positive lymphocyte proliferation index was significantly higher than the negative group. Conclusion Chronic HBV infection in pedigrees is related to the genetic polymorphisms of HLA-DQA1 and DQB1. HLA-Ⅱ may play an immunological role by affecting the ability of DCs to stimulate lymphocyte proliferation, which may be related to the chronicity of HBV infection.