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

You-Ming Chen, Yiting Li, Y. Zeng, G. Ning, Chao-shuang Lin
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Abstract

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 0.05). 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 0.05). Conclusion Immune status of the peripheral MDSC and M-MDSC can return to normal after DAA therapy in CHC patients. Key words: Hepatitis C, chronic; Direct-acting antiviral agents; Myeloid-derived suppressor cells; Immunomodulation
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直接作用抗病毒药物对慢性丙型肝炎患者髓源性抑制细胞频率的影响
目的探讨直接作用抗病毒药物(DAA)治疗对慢性丙型肝炎(CHC)患者骨髓源性抑制细胞(MDSC)及其单核细胞-骨髓源性抑癌细胞亚群(M-MDSC)频率的影响。方法选择2016年6月至2017年6月在中山大学附属第三医院接受治疗的CHC患者32例,健康对照组16例。从CHC患者的外周血中分离外周血单核细胞(PBMC),分别在DAA治疗前、DAA治疗后四周、DAA疗法后12周和DAA疗法结束后12周。流式细胞仪检测MDSC和M-MDSC的频率。采用t检验、U检验和卡方检验对数据进行分析。结果32例初治患者均获得快速病毒学应答,未发现病毒学突破。DAA治疗前,CHC患者的MDSC频率为2.18%,高于健康人(0.60%;Z=-4.593,P 0.05)。然而,在DAA治疗后12周,MDSC频率增加,与对照组相比具有静态显著性(1.64%vs 0.60%,Z=-3.117,P=0.002),与对照组比较无统计学意义(Z=1.387,P=0.664)。结论CHC患者经DAA治疗后外周MDSC和M-MDSC的免疫状态可恢复正常。关键词:丙型肝炎,慢性;直接作用的抗病毒药物;骨髓来源的抑制细胞;免疫调节
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