HIV/HCV共感染合并血友病患者利巴韦林联合干扰素治疗前后特异性细胞免疫反应的研究

摘要

Objective To study the hepatitis C virus(HCV)-specific immune responses following treatment with interferon and ribavirin in subjects with HIV-1/HCV co-infection in combination with hemophilia. Methods Immune responses were studied in a treatment trial with pegylated interferon alfa (PEG-IFN) and ribavirin(R). By using HCV core antigens,NS3 and NS5,enzyme-linked immunosorbent spots on peripheral blood mononuclear cells,products of IFN-y,IL-2,IL-4,IL-10 were measured. Immunologic,virologic and clinical variables were modeled as identifying factors associated with HCV virological response before and after 72 weeks ( SVR) treatment in 36 patients. Results There were no significant differences in baseline IFN-y and IL-2 immune responses and higher IL-10 to NS3 in subjects with VR versus non-respnnders. Subjects who had significant decreases in IL-10 responses at week 72 compared with baseline for NS3,NS5,were more likely to be VR. Using baseline immunological responses and clinical data in CART models, patients who were randomized to PEC1FN/R and had high IL-10 responses to summed HCV proteins were more likely to be VR. In SVR,IL-2 production decreased moderately, 1L-4 secreted little. The main correlation of SVR for genotype-1 subjects maintained HCV-specific IFN-7 responses from baseline to week 72. Conclusions In subjects of HIV and HCV co-infection combined with hemophilia, decrease in HCV-specific IL-10 and IL-2 responses during treatment and maintenance of IFN-y responses with IFN and ribavirin were associated with 24 or 72 week virological response.%目的 研究HIV/HCV共感染合并血友病患者在利巴韦林联合干扰素治疗过程中的细胞免疫反应,了解此类患者在抗HCV治疗过程中HCV的损伤机制和免疫重建过程.方法 收集36例HIV/HCV共感染合并血友病患者,分别在干扰素和利巴韦林治疗前、治疗结束24周后采集外周血单个核细胞( PBMC),Elispot方法检测在HCV核心抗原、NS3和NS5刺激下,检测IFN-γ、IL-2、IL-4和IL-10的分泌情况,分析细胞免疫反应与病毒应答的关系.结果 在HIV/HCV共感染患者中,治疗前非应答者IFN-γ、IL-2水平高于应答者,应答者IL-10对NS3的反应增高；治疗结束后24周应答者IL-10对HCV抗原蛋白NS3、NS5的反应显著下降,IL-2轻度下降,IFN-γ持续反应,IL-4几乎检测不到；非应答者IL-2、IFN-γ对核心抗原、NS3的反应下降,但差异无统计学意义.结论 在HIV/HCV共感染合并血友病患者中,IL-10、IL-2的下降,IFN-γ的持续反应与HCV病毒学持续应答相关,细胞因子在HCV感染的发病机制中起着重要作用.