Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia, Carrera 50 # 26-20, Bogotá, Colombia.
Clinical Research Group, Instituto Nacional de Cancerología, Calle 1 # 9-85, Bogotá, Colombia.
Sci Rep. 2020 Apr 29;10(1):7306. doi: 10.1038/s41598-020-64268-x.
Several determining factors are involved in HPV infection outcomes; human leukocyte antigen (HLA) polymorphisms have been described as related factors. This study has ascertained the effect of genetic variation on HLA-DRB1 and DQB1 genes on HPV-16/-18/-31/-33/-45 and -58 clearance and redetection in Colombian women. PCR and qPCR were used for viral identification and the Illumina MiSeq system was used for HLA-typing of cervical samples (n = 276). Survival models were adjusted for identifying alleles/haplotypes related to HPV clearance/redetection; L1/L2 protein-epitope binding to MHC-II molecules was also predicted. Significant associations suggested effects favouring or hampering clearance/redetection events depending on the viral type involved in infection, e.g. just DRB112:01:01G favoured HPV-16 (coeff: 4.8) and HPV-45 clearance (coeff: 12.65) whilst HPV-18 (coeff: 2E-15), HPV-31 (coeff: 8E-17) and HPV-58 hindered elimination (coeff: 1E-14). An effect was only observed for some alelles when configured as haplotypes, e.g. DRB104:07:01G (having the greatest frequency in the target population) was associated with DQB1*02:01:1G or *03:02:03. Epitope prediction identified 23 clearance-related peptides and 29 were redetection-related; eight might have been related to HPV-16/-18 and -58 persistence and one to HPV-18 elimination. HLA allele/haplotype relationship with the course of HPV infection (clearance/redetection) depended on the infecting HPV type, in line with the specific viral epitopes displayed.
几种决定因素涉及 HPV 感染结果；人类白细胞抗原 (HLA) 多态性已被描述为相关因素。本研究旨在确定遗传变异对 HLA-DRB1 和 DQB1 基因对 HPV-16/-18/-31/-33/-45 和 -58 清除和再检测的影响在哥伦比亚女性中。PCR 和 qPCR 用于病毒鉴定，Illumina MiSeq 系统用于宫颈样本的 HLA 分型（n=276）。生存模型用于鉴定与 HPV 清除/再检测相关的等位基因/单倍型；还预测了 L1/L2 蛋白与 MHC-II 分子的表位结合。根据感染涉及的病毒类型，显著关联表明影响有利于或阻碍清除/再检测事件，例如仅 DRB112:01:01G 有利于 HPV-16（系数：4.8）和 HPV-45 清除（系数：12.65），而 HPV-18（系数：2E-15）、HPV-31（系数：8E-17）和 HPV-58 阻碍清除（系数：1E-14）。只有当配置为单倍型时，一些等位基因才会产生影响，例如 DRB104:07:01G（在目标人群中具有最高频率）与 DQB1*02:01:1G 或 *03:02:03 相关。表位预测确定了 23 个与清除相关的肽和 29 个与再检测相关的肽；其中八个可能与 HPV-16/-18 和 -58 持续存在有关，一个与 HPV-18 消除有关。HLA 等位基因/单倍型与 HPV 感染（清除/再检测）过程的关系取决于感染的 HPV 类型，与所显示的特定病毒表位一致。
