Investigation of the HLA locus in autopsy-confirmed progressive supranuclear palsy

IF 2.5 4区 医学 Q3 IMMUNOLOGY
Jinguo Wang , Shelley L. Forrest , Sathish Dasari , Hidetomo Tanaka , Ekaterina Rogaeva , M. Carmela Tartaglia , Susan Fox , Anthony E. Lang , Subha Kalyaanamoorthy , Gabor G. Kovacs
{"title":"Investigation of the HLA locus in autopsy-confirmed progressive supranuclear palsy","authors":"Jinguo Wang ,&nbsp;Shelley L. Forrest ,&nbsp;Sathish Dasari ,&nbsp;Hidetomo Tanaka ,&nbsp;Ekaterina Rogaeva ,&nbsp;M. Carmela Tartaglia ,&nbsp;Susan Fox ,&nbsp;Anthony E. Lang ,&nbsp;Subha Kalyaanamoorthy ,&nbsp;Gabor G. Kovacs","doi":"10.1016/j.imbio.2025.152892","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>Progressive supranuclear palsy (PSP) is a neurodegenerative disease showing pathological tau accumulation in subcortical neurons and glial cells. The human leukocyte antigen (<em>HLA</em>) locus on chromosome 6 is a polymorphic region with complex linkage patterns that has been implicated in several autoimmune and neurological disorders. The <em>HLA</em> locus has not been systematically examined in PSP. It is unclear whether tau and HLA can interact to induce an autoimmune disease mechanism.</div></div><div><h3>Methods</h3><div>We evaluated an autopsy confirmed PSP cohort (<em>n</em> = 44) and compared allele/haplotype frequencies to those of the reference group of a local deceased Canadian donor pool. We performed HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions.</div></div><div><h3>Findings</h3><div>Odds ratio was 2.94 (95 % CI 1.01 to 8.55; <em>p</em> = 0.047) for <em>DQB1</em>*06:01 allele, and 2.59 (95 % CI 1.39 to 4.83; <em>p</em> = 0.0025) for the narcolepsy-associated haplotype (<em>DRB1</em>*15:01-<em>DQB1</em>*06:02). One patient with 4-repeat tau PSP-type pathology was a carrier of the IgLON5-associated haplotype (<em>DRB1</em>*10:01-<em>DQB1</em>*05:01). HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions revealed strong-binding tau peptides but not the PSP-protofilament fold for alleles DQA1*<em>01:02-DQB1*</em>06:02 and DQA1*<em>01:03-DQB1*</em>06:01.</div></div><div><h3>Conclusion</h3><div>Our study suggests that epitopes within the tau peptide may bind to HLA alleles that are found in a subset of PSP patients supporting the notion of an autoimmune pathophysiological component. These findings have implications for subtyping and stratifying patients for therapies, including those targeting immune modulation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152892"},"PeriodicalIF":2.5000,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunobiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0171298525000269","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objectives

Progressive supranuclear palsy (PSP) is a neurodegenerative disease showing pathological tau accumulation in subcortical neurons and glial cells. The human leukocyte antigen (HLA) locus on chromosome 6 is a polymorphic region with complex linkage patterns that has been implicated in several autoimmune and neurological disorders. The HLA locus has not been systematically examined in PSP. It is unclear whether tau and HLA can interact to induce an autoimmune disease mechanism.

Methods

We evaluated an autopsy confirmed PSP cohort (n = 44) and compared allele/haplotype frequencies to those of the reference group of a local deceased Canadian donor pool. We performed HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions.

Findings

Odds ratio was 2.94 (95 % CI 1.01 to 8.55; p = 0.047) for DQB1*06:01 allele, and 2.59 (95 % CI 1.39 to 4.83; p = 0.0025) for the narcolepsy-associated haplotype (DRB1*15:01-DQB1*06:02). One patient with 4-repeat tau PSP-type pathology was a carrier of the IgLON5-associated haplotype (DRB1*10:01-DQB1*05:01). HLA-Tau peptide binding prediction and modelling of HLA Class II – Tau Peptide interactions revealed strong-binding tau peptides but not the PSP-protofilament fold for alleles DQA1*01:02-DQB1*06:02 and DQA1*01:03-DQB1*06:01.

Conclusion

Our study suggests that epitopes within the tau peptide may bind to HLA alleles that are found in a subset of PSP patients supporting the notion of an autoimmune pathophysiological component. These findings have implications for subtyping and stratifying patients for therapies, including those targeting immune modulation.

Abstract Image

求助全文
约1分钟内获得全文 求助全文
来源期刊
Immunobiology
Immunobiology 医学-免疫学
CiteScore
5.00
自引率
3.60%
发文量
108
审稿时长
55 days
期刊介绍: Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信