直接抗病毒药物对慢性丙型肝炎患者外周血单个核细胞中髓源性抑制细胞表达的影响  

Effects of direct-acting antiviral agents on the frequency of myeloid-derived suppressor cells in patients with chronic hepatitis C

作　　者：陈幼明[1] 李舣婷 曾映夫 宁钢[1] 林潮双[1] Chen Youming;Li Yiting;Zeng Yingfu;Ning Gang;Lin Chaoshuang(Department of Infectious Diseases,Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou 510630,China;Department of General Medicine,Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院感染科,广州510630 [2]中山大学附属第三医院全科医学科,广州510630

出　　处：《中华传染病杂志》2019年第10期600-604,共5页Chinese Journal of Infectious Diseases

基　　金：国家自然科学基金(31370907)。

摘　　要：目的探讨直接抗病毒药物(direct-acting antiviral agents,DAA)对慢性丙型肝炎(chronic hepatitis C,CHC)患者外周血单个核细胞(peripheral blood mononuclear cells,PBMC)中髓源性抑制细胞(myeloid-derived suppressor cells,MDSC)及其亚群单核细胞样髓源性抑制细胞(monocytic myeloid-derived suppressor cells,M-MDSC)表达的影响.方法选择广州中山大学附属第三医院2016年6月至2017年6月未经治疗的32例CHC患者,同时选取16名健康志愿者作为对照.在DAA治疗前、DAA治疗4周、DAA治疗12周(即疗程结束时)和疗程结束后12周4个时间节点分别提取CHC患者PBMC,采用流式细胞术检测PBMC中MDSC及M-MDSC的频率.统计学分析采用t检验、U检验和χ^2检验.结果DAA治疗后,所有患者均获得快速病毒学应答,未出现病毒学突破.DAA治疗前,CHC患者的MDSC频率为2.18%,高于健康对照者的0.60%,差异有统计学意义(Z=-4.593,P<0.01),且MDSC频率与HCV RNA(r=0.688,P<0.01)和AST(r=0.735,P<0.01)的水平呈正相关.DAA治疗4周时,MDSC频率下降(1.07%),与健康对照者比较,差异无统计学意义(Z=-1.221,P>0.05),但DAA治疗12周时,又明显升高(1.64%),与健康对照者比较,差异有统计学意义(Z=-3.117,P=0.002),在疗程结束后12周时,再次下降到1.29%,与健康对照者比较,差异无统计学意义(Z=-1.387,P=0.664).M-MDSC的变化与其略有不同,DAA治疗前,CHC患者外周血中M-MDSC高于健康对照者(1.66%比0.81%),差异有统计学意义(Z=-2.745,P<0.01),DAA治疗4周、12周和疗程结束后12周,M-MDSC分别为0.91%、1.09%和1.10%,与健康对照者比较,差异均无统计学意义(Z=-0.589、-1.028、-0.486,均P>0.05).结论DAA治疗后,CHC患者外周血中MDSC和M-MDSC均可恢复至正常水平.Objective To investigate the effects of direct-acting antiviral agents(DAA)therapy on the frequency of myeloid-derived suppressor cells(MDSC)and their subset of monocytic myeloid-derived suppressor cells(M-MDSC)in chronic hepatitis C(CHC)patients.Methods A total of 32 treatment-naive CHC patients and 16 healthy controls were recruited at Third Affiliated Hospital of Sun Yat-Sen University from June 2016 to June 2017.The peripheral blood mononuclear cells(PBMC)were separated from the peripheral blood of patients with CHC before DAA therapy,at four weeks after DAA therapy,at 12 weeks after DAA therapy and 12 weeks after the end of DAA therapy.The frequencies of MDSC and M-MDSC were detected by the flow cytometer.The t test,U test and chi-square test was employed to analyze the data.Results All the 32 treatment-naive patients achieved the rapid virological response and no virological breakthrough was observed.Before DAA therapy,the frequency of MDSC in CHC patients was 2.18%,which was higher than healthy individuals(0.60%;Z=-4.593,P<0.01),and positively correlated with the plasma levels of hepatitis C virus(HCV)RNA(r=0.688,P<0.01)and aspartate aminotransferase(r=0.735,P<0.01).After four weeks of DAA therapy,the frequency of MDSC decreased significantly to 1.07%,with no statistical significance compared to the controls(Z=-1.221,P>0.05).However,at 12 weeks after DAA therapy,the MDSC frequency increased,with statically significance compared to the controls(1.64%vs 0.60%,Z=-3.117,P=0.002).At 12 weeks after the end of DAA therapy,the MDSC frequency had decreased to 1.29%again,with no statistical significance compared to the controls(Z=-1.387,P=0.664).The changes of M-MDSC frequency were slightly different.Before DAA therapy,the frequency of M-MDSC in CHC patients was higher compared to healthy controls(1.66%vs 0.81%,Z=-2.745,P<0.01).The frequencies of M-MDSC were 0.91%,1.09%and 1.10%at four,12 weeks after DAA and 12 weeks after the end of DAA therapy,respectively.The differences were not statistically significant compare

关 键 词：肝炎 丙型 慢性 直接抗病毒药物 髓源性抑制细胞 免疫调节 

分 类 号：R51[医药卫生—内科学]