A combination of HLA-DP α and β chain polymorphisms paired with a SNP in the DPB1 3' UTR region, denoting expression levels, are associated with atopic dermatitis.
A combination of HLA-DP α and β chain polymorphisms paired with a SNP in the DPB1 3' UTR region, denoting expression levels, are associated with atopic dermatitis.
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DOI：
10.3389/fgene.2023.1004138
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发表时间：
2023
影响因子：
3.7
通讯作者：
Monos, Dimitri S.
中科院分区：
文献类型：
--
作者：
Margolis, David J.;Duke, Jamie L.;Mitra, Nandita;Berna, Ronald A.;Hoffstad, Ole J.;Wasserman, Jenna R.;Dinou, Amalia;Damianos, Georgios;Kotsopoulou, Ioanna;Tairis, Nikolaos;Ferriola, Deborah A.;Mosbruger, Timothy L.;Hayeck, Tristan J.;Yan, Albert C.;Monos, Dimitri S.
前言：通过全基因组相关性研究，特应性皮炎(AD)的免疫反应成分，特别是人类白细胞抗原(人类白细胞抗原)II类区域的免疫反应成分已被认为与AD的病理生理学有关，但其确切成分尚未确定。方法：本研究使用下一代测序技术(NGS)检测人类白细胞抗原II类基因的遗传变异，并评估其产生的氨基酸，特别是结合位点残基，以寻找与阿尔茨海默病的关联。采用AD队列遗传学方法对464例AD患者和384例正常对照进行了HLAII类等位基因变异分析。结果：发现与HLADP、α、β等位基因及特定氨基酸有统计学意义的相关性，其中一些与AD易感性有关，另一些则具有保护作用。对DP结合口袋中的多态残基的评估表明，P1和P6(P1：α31M+(β84G或β84V)[保护]；α31Q+β84D[易感性]和P6：α11A+β11G[保护])的关键作用并在由424名AD患者组成的全国儿童队列中复制。独立地，AD易感相关残基与HLADPB1基因3‘非编码区SNP rs9277534的G多态相关，表示这些等位基因的高表达，而保护相关残基与A多态相关，表示低表达。讨论：这些发现为评估怀疑与AD相关的非自身抗原奠定了基础，因为它们可能与特定的HLAII类亚组分相互作用，形成参与AD病理生理学的复合体。人类白细胞抗原-DP的结构成分和这些成分的表达水平共同参与了AD的病理生理过程。
Introduction: Components of the immune response have previously been associated with the pathophysiology of atopic dermatitis (AD), specifically the Human Leukocyte Antigen (HLA) Class II region via genome-wide association studies, however the exact elements have not been identified. Methods: This study examines the genetic variation of HLA Class II genes using next generation sequencing (NGS) and evaluates the resultant amino acids, with particular attention on binding site residues, for associations with AD. The Genetics of AD cohort was used to evaluate HLA Class II allelic variation on 464 subjects with AD and 384 controls. Results: Statistically significant associations with HLA-DP α and β alleles and specific amino acids were found, some conferring susceptibility to AD and others with a protective effect. Evaluation of polymorphic residues in DP binding pockets revealed the critical role of P1 and P6 (P1: α31M + (β84G or β84V) [protection]; α31Q + β84D [susceptibility] and P6: α11A + β11G [protection]) and were replicated with a national cohort of children consisting of 424 AD subjects. Independently, AD susceptibility-associated residues were associated with the G polymorphism of SNP rs9277534 in the 3’ UTR of the HLA-DPB1 gene, denoting higher expression of these HLA-DP alleles, while protection-associated residues were associated with the A polymorphism, denoting lower expression. Discussion: These findings lay the foundation for evaluating non-self-antigens suspected to be associated with AD as they potentially interact with particular HLA Class II subcomponents, forming a complex involved in the pathophysiology of AD. It is possible that a combination of structural HLA-DP components and levels of expression of these components contribute to AD pathophysiology.
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影响因子：
2.6
作者：
Gough SC;Simmonds MJ
通讯作者：
Simmonds MJ
影响因子：
14.2
作者：
Davidson, Wendy F.;Leung, Donald Y. M.;Plaut, Marshall
通讯作者：
Plaut, Marshall
影响因子：
2.7
作者：
Margolis DJ;Mitra N;Kim B;Gupta J;Hoffstad OJ;Papadopoulos M;Wubbenhorst B;Nathanson KL;Duke JL;Monos DS;Kamoun M
通讯作者：
Kamoun M
影响因子：
4.4
作者：
Castelli, FA;Buhot, C;Maillère, B
通讯作者：
Maillère, B
DOI：
10.1073/pnas.1001772107
发表时间：
2010-04-20
影响因子：
11.1
作者：
Dai, Shaodong;Murphy, Guinevere A.;Fontenot, Andrew P.
通讯作者：
Fontenot, Andrew P.