Department of Hepatology, Division of Medicine, Imperial College London, United Kingdom.
Gastroenterology. 2011 Jul;141(1):320-5, 325.e1-2. doi: 10.1053/j.gastro.2011.04.005. Epub 2011 Apr 14.
BACKGROUND & AIMS: Polymorphisms in the interleukin-28B (IL28B) gene are associated with outcomes from infection with hepatitis C virus (HCV). However, the role of these polymorphisms in protecting injection drug users who are at high risk for HCV infection but do not have detectable antibodies against HCV or HCV RNA (exposed uninfected) has not been demonstrated. We investigated whether these individuals have the IL28B genotype rs12979860-CC, which protects some individuals against HCV infection.
Seventy-four exposed uninfected individuals, 89 spontaneous resolvers, and 234 chronically infected individuals were genotyped to determine single nucleotide polymorphisms at IL28B.rs12979860.
Exposed, uninfected individuals had a significantly lower frequency of the protective genotype (rs12979860-CC) than anti-HCV-positive spontaneous resolvers (41.9% vs 69.7%, respectively; P=.0005; odds ratio [OR], 0.31; 95% confidence interval [CI]: 0.16-0.60) but a similar frequency to patients who were chronically infected (41.9% vs 43.6%, respectively; P=ns). However, exposed, uninfected individuals had a significantly higher frequency of homozygosity for killer cell immunoglobulin-like receptor 2DL3:group 1 HLA-C (KIR2DL3:HLA-C1) than those with chronic infection (31.1% vs 13.3%, respectively; P=.0008; OR, 2.95; 95% CI: 1.59-5.49). For patients who spontaneously resolved infection, IL28B and KIR:HLA protected, independently, against chronic HCV infection, based on logistic regression and synergy analyses (synergy factor, 1.3; 95% CI: 0.37-4.75; P synergy=.6).
IL28B and KIR2DL3:HLA-C1 are independently associated with spontaneous resolution of viremia following HCV exposure. Resistance to HCV infection in exposed uninfected cases is associated with homozygosity for KIR2DL3:HLA-C1 but not the single nucleotide polymorphism IL28B.rs12979860. Uninfected individuals are therefore a distinct population from patients who spontaneously resolve HCV infection. Distinct, nonsynergistic innate immune mechanisms can determine outcomes of HCV exposure.
白细胞介素 28B（IL28B）基因的多态性与丙型肝炎病毒（HCV）感染的结果相关。然而，这些多态性在保护那些感染 HCV 但未检测到 HCV 抗体或 HCV RNA（暴露未感染）的高风险注射吸毒者方面的作用尚未得到证实。我们研究了这些个体是否具有 IL28B 基因型 rs12979860-CC，该基因型可保护某些个体免受 HCV 感染。
对 74 名暴露未感染个体、89 名自发清除者和 234 名慢性感染个体进行基因分型，以确定 IL28B.rs12979860 处的单核苷酸多态性。
暴露未感染个体保护性基因型（rs12979860-CC）的频率明显低于抗 HCV 阳性自发清除者（分别为 41.9%和 69.7%；P=.0005；比值比[OR]，0.31；95%置信区间[CI]：0.16-0.60），但与慢性感染者相似（分别为 41.9%和 43.6%；P=ns）。然而，暴露未感染个体的杀伤细胞免疫球蛋白样受体 2DL3：组 1 HLA-C（KIR2DL3：HLA-C1）纯合子频率明显高于慢性感染者（分别为 31.1%和 13.3%；P=.0008；OR，2.95；95%CI：1.59-5.49）。对于自发清除感染的患者，IL28B 和 KIR：HLA 独立地保护他们免受慢性 HCV 感染，基于逻辑回归和协同分析（协同因子，1.3；95%CI：0.37-4.75；P 协同=.6）。
IL28B 和 KIR2DL3：HLA-C1 与 HCV 暴露后自发清除病毒血症独立相关。暴露未感染病例中对 HCV 感染的抵抗力与 KIR2DL3：HLA-C1 纯合子有关，而与单核苷酸多态性 IL28B.rs12979860 无关。因此，未感染个体与自发清除 HCV 感染的患者是不同的人群。不同的、非协同的先天免疫机制可以决定 HCV 暴露的结果。
