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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Consistent beneficial effects of killer cell immunoglobulin-like receptor 2DL3 and group 1 human leukocyte antigen-C following exposure to hepatitis C virus.
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Consistent beneficial effects of killer cell immunoglobulin-like receptor 2DL3 and group 1 human leukocyte antigen-C following exposure to hepatitis C virus.

机译：暴露于丙型肝炎病毒后，杀伤细胞免疫球蛋白样受体2DL3和第1组人类白细胞抗原C的一致有益作用。

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Natural killer cells are a key component in the immune control of viral infections. Their functions are controlled by inhibitory receptors for major histocompatability complex (MHC) class I, including the killer cell immunoglobulin-like receptors (KIR). KIR2DL3 in combination with its cognate human leukocyte antigen (HLA)-C ligand has been shown to be associated with spontaneous resolution of viremia following hepatitis C virus (HCV) infection. In order to determine if this gene combination is advantageous across all potential outcomes following HCV exposure, we studied individuals with apparent resistance to HCV infection who remain seronegative and aviremic despite long-term injection drug use and also individuals chronically infected with HCV who successfully clear HCV with treatment. Homozygosity for KIR2DL3 in combination with group 1 HLA-C allotypes was more frequent in exposed seronegative aviremic individuals as compared to those with chronic HCV (25.0% versus 9.7%, P = 0.003, odds ratio [OR] = 3.1, 95% confidence interval [CI] = 1.3-7.1) in a model similar to that found for those spontaneously resolving HCV. In individuals undergoing treatment for HCV, those with KIR2DL3 and group 1 HLA-C were more likely to make a sustained virological response (SVR) (P = 0.013, OR = 2.3, 95% CI = 1.1-4.5). KIR and HLA-C protection in both treatment response and spontaneously resolving HCV was validated at the allelic level, in which KIR2DL3-HLA-Cw*03 was associated with SVR (P = 0.004, OR = 3.4, 95% CI = 1.5-8.7) and KIR2DL3/KIR2DL3-HLA-Cw*03 was associated with spontaneous resolution of HCV infection (P = 0.01, OR = 2.3, 95% CI = 1.2-4.4). Conclusion: KIR and HLA-C genes are consistently beneficial determinants in the outcome of HCV infection. This advantage extends to the allelic level for both gene families.
机译：天然杀伤细胞是病毒感染免疫控制的关键组成部分。它们的功能受I类主要组织相容性复合物（MHC）的抑制性受体控制，包括杀伤细胞免疫球蛋白样受体（KIR）。 KIR2DL3及其相关的人类白细胞抗原（HLA）-C配体结合已被证明与丙型肝炎病毒（HCV）感染后病毒血症的自发消退有关。为了确定该基因组合是否在HCV暴露后的所有潜在结果中均具有优势，我们研究了对HCV感染具有明显抵抗力的个体，尽管长期注射毒品仍保持血清阴性和鸟血症，以及长期感染HCV且成功清除HCV的个体治疗。与慢性HCV感染者相比，暴露于血清阴性的鸟取血症个体中KIR2DL3与第1组HLA-C同种异型的纯合性更为频繁（25.0％比9.7％，P = 0.003，优势比[OR] = 3.1，95％置信区间[CI] = 1.3-7.1）的模型与自发解决HCV的模型相似。在接受HCV治疗的个体中，具有KIR2DL3和1组HLA-C的个体更有可能产生持续的病毒学应答（SVR）（P = 0.013，OR = 2.3，95％CI = 1.1-4.5）。在等位基因水平上验证了KIR和HLA-C在治疗反应和自发解决HCV方面的保护作用，其中KIR2DL3-HLA-Cw * 03与SVR相关（P = 0.004，OR = 3.4，95％CI = 1.5-8.7 ）和KIR2DL3 / KIR2DL3-HLA-Cw * 03与HCV感染的自发消退相关（P = 0.01，OR = 2.3，95％CI = 1.2-4.4）。结论：KIR和HLA-C基因始终是HCV感染结果的有益决定因素。该优势扩展到两个基因家族的等位基因水平。

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