Occupational Exposure to Hepatitis C Virus: Early T-Cell Responses in the Absence of Seroconversion in a Longitudinal Cohort Study
Occupational Exposure to Hepatitis C Virus: Early T-Cell Responses in the Absence of Seroconversion in a Longitudinal Cohort Study
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DOI：
10.1093/infdis/jit270
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发表时间：
2013-09-15
影响因子：
6.4
通讯作者：
Rehermann, Barbara
中科院分区：
文献类型：
--
作者：
Heller, Theo;Werner, Jens Martin;Rehermann, Barbara
背景。尽管经常接触丙型肝炎病毒 (HCV)，但血清阴性患者的 T 细胞反应已被描述为丙型肝炎病毒 (HCV) RNA 检测呈阴性。然而，这些研究的横断面设计并没有阐明T细胞是否确实是由低水平HCV暴露诱导而没有血清转化，或者它们是否是由常规急性感染和随后的抗体损失引起的。方法。我们的纵向研究历时 10 年，招募了 72 名有丙肝病毒暴露记录的医护人员。我们纵向研究了病毒血症、抗体和 T 细胞反应 6 个月。结果。所有医护人员的 HCV RNA 和抗体均呈阴性。然而，48% 的人产生了增殖性 T 细胞反应，42% 的人在干扰素-γ 酶联免疫吸附斑点测定中产生了反应，并使用 29 名未暴露于 HCV 的健康对照来定义测定截止值。反应率与传播风险评分相关。 T 细胞反应在第 4 周达到峰值，并在暴露后第 12 周恢复到基线。它们主要针对非结构性 HCV 蛋白，这些蛋白不是 HCV 颗粒的一部分，因此一定是在受感染的细胞中合成的。结论。 HCV 的亚临床传播经常发生，导致感染和非结构蛋白的合成，尽管无法检测到全身病毒血症。 T 细胞反应是比抗体更敏感的低水平 HCV 暴露指标。
Background. T-cell responses have been described in seronegative patients who test negative for hepatitis C virus (HCV) RNA despite frequent HCV exposure. However, the cross-sectional design of those studies did not clarify whether T cells were indeed induced by low-level HCV exposure without seroconversion or whether they resulted from regular acute infection with subsequent antibody loss.Methods. Over a 10-year period, our longitudinal study recruited 72 healthcare workers with documented HCV exposure. We studied viremia and antibody and T-cell responses longitudinally for 6 months.Results. All healthcare workers remained negative for HCV RNA and antibodies. However, 48% developed proliferative T-cell response and 42% developed responses in interferon-gamma enzyme-linked immunosorbent spot assays, with 29 healthy HCV-unexposed controls used to define assay cutoffs. The response prevalence was associated with the transmission risk score. T-cell responses peaked at week 4 and returned to baseline by week 12 after exposure. They predominantly targeted nonstructural HCV proteins, which are not part of the HCV particle and thus must have been synthesized in infected cells.Conclusions. Subclinical transmission of HCV occurs frequently, resulting in infection and synthesis of nonstructural proteins despite undetectable systemic viremia. T-cell responses are more sensitive indicators of this low-level HCV exposure than antibodies.