Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland; Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), Frederick National Laboratory for Cancer Research, Frederick, Maryland.
J Med Virol. 2015 Apr;87(4):544-52. doi: 10.1002/jmv.24089. Epub 2015 Jan 21.
Hepatitis C (HCV) treatment for patients coinfected with human immunodeficiency virus (HIV) and HCV is associated with modest rates of sustained virologic response (SVR) and an increased rate of relapse when compared to HCV monoinfected patients. As patients who attain SVR and patients who relapse are clinically indistinguishable during treatment, where both groups have fully suppressed HCV viral load, it has not been possible to identify in advance those who will relapse. Biomarkers that may distinguish patients with differential treatment response may be clinically useful and provide insight into mechanisms of relapse. In this retrospective study, serum and PBMCs were obtained from 41 HIV/HCV co-infected patients and 17 healthy volunteers. Changes in antibody titers to various regions of the HCV proteome during treatment for HCV were determined using a novel luciferase immunoprecipitation assay. Changes in B-cell subtypes in patients with differential treatment response as well as healthy volunteers were compared. This study demonstrates that elevated anti-HCV core antibody titers persisted during HCV treatment in patients who relapsed when compared to those who attained SVR. Furthermore, characterization of B cells in patients who relapsed demonstrated an abnormal B-cell phenotype distribution characterized by elevated frequencies of exhausted B cells among relapsers at baseline, which persisted despite suppression of HCV viremia at 24 weeks, along with increased frequencies of plasmablasts. These data suggest that anti-HCV specific B cells may be responding to ongoing subclinical HCV replication in patients who will relapse.
丙型肝炎（HCV）治疗合并人类免疫缺陷病毒（HIV）和 HCV 感染的患者，与 HCV 单感染患者相比，持续病毒学应答（SVR）的比例较低，复发率较高。由于达到 SVR 的患者和复发的患者在治疗期间的临床特征无明显差异，因为两组患者的 HCV 病毒载量都完全得到抑制，因此无法提前确定谁会复发。能够区分患者不同治疗反应的生物标志物可能具有临床应用价值，并深入了解复发的机制。在这项回顾性研究中，从 41 例 HIV/HCV 合并感染患者和 17 例健康志愿者中获得了血清和 PBMCs。使用新型荧光素酶免疫沉淀检测法，检测了 HCV 治疗过程中 HCV 蛋白组不同区域的抗体滴度变化。比较了具有不同治疗反应的患者和健康志愿者的 B 细胞亚群变化。本研究表明，与获得 SVR 的患者相比，复发患者的 HCV 治疗期间抗 HCV 核心抗体滴度持续升高。此外，对复发患者 B 细胞的特征分析表明，异常的 B 细胞表型分布特征是复发患者中耗竭 B 细胞的频率升高，尽管在 24 周时 HCV 病毒血症得到抑制，但仍持续存在，同时浆母细胞的频率增加。这些数据表明，抗 HCV 特异性 B 细胞可能对即将复发的患者亚临床 HCV 复制做出反应。
