Department of Clinical Immunology, University Hospital Alexandrovska, Medical University, Sofia, Bulgaria.
Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA; Histocompatibility, Immunogenetics and Disease Profiling Laboratory, Stanford Blood Center, Palo Alto, CA, USA.
Hum Immunol. 2019 Sep;80(9):703-713. doi: 10.1016/j.humimm.2019.07.287. Epub 2019 Jul 20.
The 'Immunogenetics of Aging' project is a component introduced in the 14th International HLA and Immunogenetics Workshop (IHIW) and developed further within subsequent workshops. The aim was to determine the relevance of immunogenetic markers, focusing on HLA, cytokine genes, and some innate immunity genes, for successful aging and an increased capacity to reach the extreme limits of life-span. Within the 17th IHIW we applied Next Generation Sequencing methods to refine further HLA associations at allele level in longevity, and to extend our knowledge to additional loci such as HLA-DQA1, HLA-DPB1 and HLA-DPA1. Analysis of relatively small number of healthy elderly and young controls from four populations showed that some HLA class I and class II alleles were significantly positively associated with healthy aging. Additionally we observed statistically significant differences in HLA allele distribution when the analysis was performed separately in elderly females and males compared to sex-matched young controls. Haplotypes, probably associated with better control of viral and malignant diseases were increased in the elderly sample. These preliminary NGS data could confirm our hypotheses that survival and longevity might be associated with selection of HLA alleles and haplotypes conferring disease resistance or susceptibility. Therefore HLA alleles and haplotypes could be informative immunogenetic markers for successful ageing.
“衰老的免疫遗传学”项目是在第十四届国际 HLA 和免疫遗传学研讨会（IHIW）中引入的一个组成部分，并在随后的研讨会上进一步发展。其目的是确定免疫遗传标记物的相关性，重点关注 HLA、细胞因子基因和一些先天免疫基因，以实现成功的衰老和增加达到寿命极限的能力。在第十七届 IHIW 中，我们应用下一代测序方法，进一步细化了与长寿相关的 HLA 等位基因关联，并将我们的知识扩展到其他基因座，如 HLA-DQA1、HLA-DPB1 和 HLA-DPA1。对来自四个群体的相对少量的健康老年人和年轻对照者进行的分析表明，一些 HLA Ⅰ类和Ⅱ类等位基因与健康衰老显著正相关。此外，当我们对老年女性和男性与同龄年轻对照组分别进行分析时，我们观察到 HLA 等位基因分布存在统计学差异。在老年样本中，可能与更好地控制病毒和恶性疾病相关的单体型增加。这些初步的 NGS 数据可以证实我们的假设，即生存和长寿可能与赋予疾病抗性或易感性的 HLA 等位基因和单体型的选择相关。因此，HLA 等位基因和单体型可能是成功衰老的有用免疫遗传标记物。
