Association of Killer Cell Immunoglobulin-like Receptors with Spontaneous Clearance of Hepatitis C Virus in the Chinese Population
Association of Killer Cell Immunoglobulin-like Receptors with Spontaneous Clearance of Hepatitis C Virus in the Chinese Population
复制标题
中国人群杀伤细胞免疫球蛋白样受体与丙型肝炎病毒自发清除的关系
作者：
单振刚;黄杰庭;廖峭;黄珂;王敏;许茹;汤曦;张卫云;付涌水;黎诚耀;戎霞
自然杀伤（NK）细胞是对病毒感染的先天免疫反应的关键组成部分。杀伤细胞免疫球蛋白样受体（KIR）参与调节NK细胞激活或抑制功能的平衡。然而，在中国人群中，KIR与丙型肝炎病毒（HCV）自发清除的相关性尚不清楚。研究设计和方法共招募了407名HCV血清阳性自愿献血者，其中203名自发清除病毒，204名慢性感染。通过使用序列特异性引物的聚合酶链反应单独检测KIR基因的存在。结果表明，HCV清除组中KIR 2DL 2、2DS 2、2DL 2/2DL 3和2DL 5A-/2DL 5 B+基因型频率高于慢性感染组（比值比[OR]，1.640，p = 0.034; OR，1.664，p=0.032; OR，1.636，p=0.040; OR，2.601，p=0.012）。多因素Logistic回归分析显示，KIR 2DL 5A-/2DL 5 B+与HCV清除相关（OR，2.448，p=0.027），与性别、IL 28 B和其他KIR无关。相比之下，发现KIR 2DL 3/2DL 3（OR，0.610，p=0.034）以及2DL 3/2DL 3 + HLA-C1或C1 C1（OR，0.580，p=0.017; OR，0.639，p=0.025）与慢性HCV感染相关。在IL-28 B的作用下，KIR-2DL-3（含或不含HLA配体）的存在增加了慢性HCV感染的风险。结论：本研究中，我们发现KIR-2DL-5A-/2DL-5 B+与HCV自发清除相关，而KIR-2DL-3/2DL-3、2DL-3/2DL-3 +HLA-C1或C1-C1与慢性感染相关。我们的研究强调了这样一个事实，即KIR和KIR-HLA的作用有助于通过先天免疫应答控制HCV感染。
BACKGROUNDNatural killer (NK) cells are critical components in innate immune response to viral infection. Killer cell immunoglobulin‐like receptors (KIRs) are involved in regulating the balance of activation or inhibitory function of NK cells. However, the association of KIRs with the spontaneous clearance of hepatitis C virus (HCV) remains unclear in the Chinese population.STUDY DESIGN AND METHODSA total of 407 HCV‐seropositive voluntary blood donors were recruited, including 203 with spontaneous viral clearance and 204 with chronic infection. The presence of KIR genes was detected individually by polymerase chain reaction with sequence‐specific primers. Data of HLA andinterleukin‐28B(IL28B) genotypes were extracted from our previous study.RESULTSOur results showed thatKIR2DL2, 2DS2, 2DL2/2DL3,and2DL5A–/2DL5B+were more frequent in subjects with HCV clearance than those with chronic infection (odds ratio [OR], 1.640, p = 0.034; OR, 1.664, p=0.032; OR, 1.636, p=0.040; and OR, 2.601, p=0.012, respectively). Multivariate logistic regression analysis showed thatKIR2DL5A–/2DL5B+associated with HCV clearance (OR, 2.448, p=0.027), independent of sex,IL28B,and otherKIRs. In contrast,KIR2DL3/2DL3(OR, 0.610, p=0.034) as well as2DL3/2DL3+HLA‐C1 or C1C1 (OR, 0.580, p=0.017; and OR, 0.639, p=0.025, respectively) was found associated with chronic HCV infection. The presence of the homozygousKIR2DL3with or without its HLA ligand increased the OR of developing chronic HCV infection in the context ofIL28B.CONCLUSIONSIn this study we identifiedKIR2DL5A–/2DL5B+associated with HCV spontaneous clearance, whileKIR2DL3/2DL3,2DL3/2DL3+HLA‐C1, or C1C1 associated with chronic infection. Our study highlighted the fact that the roles of KIR and KIR‐HLA contributed to the control of HCV infection by innate immune responses.