{"title":"Exploring the HLA complex in autoimmunity: From the risk haplotypes to the modulation of expression","authors":"Silvia Sartoris , Giovanna Del Pozzo","doi":"10.1016/j.clim.2024.110266","DOIUrl":null,"url":null,"abstract":"<div><p>The genes mapping at the HLA region show high density, strong linkage disequilibrium and high polymorphism, which affect the association of HLA class I and class II genes with autoimmunity. We focused on the HLA haplotypes, genomic structures consisting of an array of specific alleles showing some degrees of genetic association with different autoimmune disorders. GWASs in many pathologies have identified variants in either the coding loci or the flanking regulatory regions, both in linkage disequilibrium in haplotypes, that are frequently associated with increased risk and may influence gene expression. We discuss the relevance of the HLA gene expression because the level of surface heterodimers determines the number of complexes presenting self-antigen and, thus, the strength of pathogenic autoreactive T cells immune response.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003759/pdfft?md5=7cd06c6f943cee63d821e9d1f86f0600&pid=1-s2.0-S1521661624003759-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521661624003759","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The genes mapping at the HLA region show high density, strong linkage disequilibrium and high polymorphism, which affect the association of HLA class I and class II genes with autoimmunity. We focused on the HLA haplotypes, genomic structures consisting of an array of specific alleles showing some degrees of genetic association with different autoimmune disorders. GWASs in many pathologies have identified variants in either the coding loci or the flanking regulatory regions, both in linkage disequilibrium in haplotypes, that are frequently associated with increased risk and may influence gene expression. We discuss the relevance of the HLA gene expression because the level of surface heterodimers determines the number of complexes presenting self-antigen and, thus, the strength of pathogenic autoreactive T cells immune response.
映射在 HLA 区域的基因显示出高密度、强连锁不平衡和高多态性,这影响了 HLA I 类和 II 类基因与自身免疫的关联。我们的研究重点是 HLA 单倍型,它是由一系列特定等位基因组成的基因组结构,与不同的自身免疫性疾病有一定程度的遗传关联。对许多病症进行的全球基因组研究发现,编码基因位点或侧翼调控区域的变异(两者在单倍型中处于连锁不平衡状态)经常与风险增加有关,并可能影响基因表达。我们讨论了 HLA 基因表达的相关性,因为表面异质二聚体的水平决定了呈现自身抗原的复合物的数量,从而决定了致病性自反应 T 细胞免疫反应的强度。
期刊介绍:
Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.