KIR3DS1/HLA-B Bw4-80Ile Genotype Is Correlated with the IFN-α Therapy Response in hepatitis B e antigen-Positive Chronic Hepatitis B.
KIR3DS1/HLA-B Bw4-80Ile Genotype Is Correlated with the IFN-α Therapy Response in hepatitis B e antigen-Positive Chronic Hepatitis B.
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Kir3Ds1/HLA-B Bw4-80lle 基因型与乙型肝炎 e 抗原阳性慢性乙型肝炎的 IFN-α 治疗反应相关
DOI：
10.3389/fimmu.2017.01285
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发表时间：
2017
影响因子：
7.3
通讯作者：
Wei H
中科院分区：
文献类型：
--
作者：
Li W;Shen X;Fu B;Guo C;Liu Y;Ye Y;Sun R;Li J;Tian Z;Wei H
到目前为止，已经报道了几个治疗水平的病毒学和血清学指标可以预测干扰素-α的应答。然而，还没有发现有效的预测因素，如药物反应基因，可以在使用干扰素-α进行抗乙肝病毒治疗之前检测到。在各种各样的慢性病毒感染中，影响人类免疫的基因在理解宿主和病毒的共同进化方面发挥着重要作用。杀伤细胞免疫球蛋白样受体(KIRS)在等位基因和单倍型水平上具有高度的多态性，当NK细胞与靶细胞上的人类白细胞抗原(HL A)I类分子相互作用时，KIR通过微调抑制和激活NK细胞反应参与NK细胞的抗病毒功能。对于每个个体，KIR和人类白细胞抗原配体的配对是由基因决定的。我们对119例e抗原(HBe)阳性的慢性乙型肝炎患者进行了α基因分型，以探讨特定的KIR和HLA谱是否影响乙肝病毒感染的风险和对干扰素-HBe治疗的应答。这些患者包括43例干扰素-α治疗48 周后持续有效(SR)的患者、76例无反应(NR)的患者和96例健康对照。SR定义为治疗后24 周(72周)HBVdna DNA阴转率为2,000 IU/ml，丙氨酸氨基转移酶复常者为HBe Ag阴转者。在这项研究中，我们发现激活KIR基因在中国汉族人，特别是在患有慢性乙型肝炎的汉族人中比在高加索人中更少见。此外，KIR3DS1基因与人类白细胞抗原-B基因Bw4-80Ile相结合，对接受干扰素-α治疗的慢性乙型肝炎患者的疗效有很大影响。KIR3DS1和HLABbw4-80Ile基因组合频率在持续治疗有效的患者中高于未缓解患者[35.3vs1.3%；优势比(OR) = 19.85；P = 0.0008]。激活KIR3DS1和HLABBBW4-80Ile可协同预测HBe Ag阳性慢性乙肝患者SR为干扰素-α。对KIR3DS1基因和HLABBbw4-80Ile等位基因进行基因分型可能有助于医生选择干扰素-α治疗乙肝病毒的最佳候选者。
To date, several on-treatment-level virological and serological indices that may predict the response to interferon alpha (IFN-α) have been reported. However, no effective predictors, such as drug–response genes, that can be detected before administration of anti-hepatitis B virus (HBV) therapy with IFN-α, have been found. In the diverse range of chronic viral infection, genes that affect human immunity play important roles in understanding host and viral co-evolution. Killer-cell immunoglobulin-like receptors (KIRs), which are highly polymorphic at the allele and haplotype levels, participate in the antiviral function of natural killer (NK) cells via fine-tuning inhibition and activation of NK-cell responses that occur when the NK cells interact with human leukocyte antigen (HLA) class I molecules on target cells. For each individual, the pairing of KIR and HLA ligand is genetically determined. To investigate whether a particular KIR and HLA repertoire influences the risk of HBV infection and response to IFN-α treatment for chronic hepatitis B (CHB), we genotyped the KIRs and HLA ligands of 119 hepatitis B e antigen (HBeAg)-positive CHB patients. These patients included 43 patients who achieved sustained response (SR) induced by IFN-α treatment for 48 weeks, 76 patients who achieved no response (NR), and 96 healthy subjects as controls. SR was defined as HBeAg loss with HBV DNA < 2,000 IU/ml and alanine aminotransferase normalization at 24 weeks posttreatment (week 72). In this study, we showed that activating KIR genes were less prevalent in Han Chinese, especially in Han Chinese with CHB, than in Caucasians. Furthermore, the KIR3DS1 gene, in combination with HLA-B Bw4-80Ile, strongly influenced the therapeutic outcomes for CHB patients who were treated with IFN-α. The frequency of the combination of genes encoding KIR3DS1 and HLA-B Bw4-80Ile was higher in patients who had a sustained treatment response than in patients who had NR [35.3 versus 1.3%; odds ratio (OR) = 19.85; P = 0.0008]. Activating KIR3DS1 and HLA-B Bw4-80Ile synergistically predicted SR to IFN-α for HBeAg-positive CHB patients. Genotyping for the KIR3DS1 gene and the HLA-B Bw4-80Ile allele might help physicians choose the optimal candidates for anti-HBV treatment with IFN-α.
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影响因子：
30.8
作者：
Martin, MP;Gao, XJ;Carrington, M
通讯作者：
Carrington, M
影响因子：
2.4
作者：
Franco, Elisabetta;Bagnato, Barbara;Zaratti, Laura
通讯作者：
Zaratti, Laura
DOI：
10.1084/jem.181.3.1133
发表时间：
1995-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gumperz JE;Litwin V;Phillips JH;Lanier LL;Parham P
通讯作者：
Parham P
影响因子：
5
作者：
Jones, D. C.;Edgar, R. S.;Young, N. T.
通讯作者：
Young, N. T.
影响因子：
4.4
作者：
Carr, William H.;Rosen, David B.;Lanier, Lewis L.
通讯作者：
Lanier, Lewis L.