Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
Hum Immunol. 2010 Aug;71(8):804-8. doi: 10.1016/j.humimm.2010.05.011. Epub 2010 May 17.
Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) affects approximately 5% of HTLV-1-infected individuals. It is poorly understood why only some infected subjects develop this disease, but host genetic factors may determine susceptibility. The innate immune system may influence disease outcome in HTLV-1-infected individuals because of its role in early immune responses to viral infections. Variation in genes encoding killer cell immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) molecule ligands may affect the risk of HAM/TSP. We performed a two-stage case-control study to examine the distribution of KIR genes and HLA-Cw groups in Peruvian HTLV-1-infected HAM/TSP individuals and asymptomatic carriers. We also tested for epistatic effects between specific KIR genes and HLA-Cw groups. In the first stage, we found several trends toward association with HAM/TSP or proviral load (PVL). However, these results were not replicated in the second stage. In conclusion, this is the first report on KIR gene frequencies in the Peruvian population and may be of significance in hematopoietic stem-cell transplants. Our study did not reveal significant associations between KIR genes and HLA-Cw groups and HAM/TSP or PVL. However, because our study was powered to detect only larger effects, additional studies using larger cohorts are needed.
人类 T 淋巴细胞白血病病毒 1(HTLV-1)相关脊髓病/热带痉挛性截瘫(HAM/TSP)影响大约 5%的 HTLV-1 感染者。目前尚不清楚为什么只有部分感染者会患上这种疾病,但宿主遗传因素可能决定了易感性。固有免疫系统可能会影响 HTLV-1 感染者的疾病结局,因为它在病毒感染的早期免疫反应中发挥作用。杀伤细胞免疫球蛋白样受体(KIR)和其人类白细胞抗原(HLA)分子配体的基因变异可能会影响 HAM/TSP 的风险。我们进行了一项两阶段病例对照研究,以研究秘鲁 HTLV-1 感染的 HAM/TSP 个体和无症状携带者中 KIR 基因和 HLA-Cw 组的分布情况。我们还检测了特定 KIR 基因和 HLA-Cw 组之间的上位效应。在第一阶段,我们发现了一些与 HAM/TSP 或前病毒载量(PVL)相关的趋势。然而,这些结果在第二阶段没有得到复制。总之,这是关于秘鲁人群中 KIR 基因频率的首次报道,可能对造血干细胞移植具有重要意义。我们的研究没有发现 KIR 基因和 HLA-Cw 组与 HAM/TSP 或 PVL 之间存在显著关联。然而,由于我们的研究仅能检测到更大的效应,因此需要使用更大的队列进行进一步研究。