Di Bona D, Aiello A, Colomba C, Bilancia M, Accardi G, Rubino R, Giannitrapani L, Tuttolomondo A, Cascio A, Caiaffa M F, Rizzo S, Di Lorenzo G, Candore G, Duro G, Macchia L, Montalto G, Caruso C
Dipartimento dell'Emergenza e dei Trapianti d'Organo, Università di Bari Aldo Moro, Bari, Italy.
Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
J Viral Hepat. 2017 Sep;24(9):768-775. doi: 10.1111/jvh.12698. Epub 2017 May 5.
Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIR and HLA loci are highly polymorphic, and certain HLA-KIR combinations have been found to protect against viral infections. In this study, we analysed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA-A-Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude OR, 4.67; P<.001) and HC (10%) (crude OR, 12.38; P<.001). Similar results were obtained for the HLA-C2 ligand group, more frequent in CHB (84%), than subjects with resolved infection (70%) (crude OR, 2.24; P<.10) and HC (60%) (crude OR, 3.56; P<.01). Conversely, the frequency of KIR2DL3 was lower in CHB (81%) than in subjects with resolved infection (98%) (crude OR, 0.10; P<.05). These results suggest a detrimental role of HLA-A-Bw4 and HLA-C2 groups, which are associated with the development of CHB, and a protective role of KIR2DL3. A stepwise variable selection procedure, based on multiple logistic regression analysis, identified these three predictive variables as the most relevant, featuring high specificity (90.9%) and positive predictive value (87.5%) for the development of CHB. Our results suggest that a combination of KIR/HLA gene/alleles is able to predict the outcome of HBV infection.
杀伤细胞免疫球蛋白样受体（KIRs）通过与人类白细胞抗原（HLA）相互作用来调节自然杀伤细胞的激活。KIR和HLA基因座具有高度多态性，并且已发现某些HLA-KIR组合可预防病毒感染。在本研究中，我们分析了KIR/HLA谱是否可能影响乙型肝炎病毒（HBV）感染的进程。对57例慢性乙型肝炎（CHB）患者、44例已清除HBV感染的患者和60例健康未感染对照（HC）进行了KIR及其HLA配体的基因分型。CHB患者中HLA-A-Bw4配体组的频率（58%）高于已清除感染的患者（23%）（粗比值比，4.67；P<0.001）和HC（10%）（粗比值比，12.38；P<0.001）。对于HLA-C2配体组也获得了类似结果，CHB患者中该配体组更常见（84%），高于已清除感染的患者（70%）（粗比值比，2.24；P<0.10）和HC（60%）（粗比值比，3.56；P<0.01）。相反，CHB患者中KIR2DL3的频率（81%）低于已清除感染的患者（98%）（粗比值比，0.10；P<0.05）。这些结果表明HLA-A-Bw4和HLA-C2组与CHB的发生相关，具有有害作用，而KIR2DL3具有保护作用。基于多因素逻辑回归分析的逐步变量选择程序确定这三个预测变量最为相关，对CHB的发生具有高特异性（90.9%）和阳性预测值（87.5%）。我们的结果表明，KIR/HLA基因/等位基因的组合能够预测HBV感染的结果。
