Xiaofan Jia, Janet M Wenzlau, Caiguo Zhang, Fran Dong, Kathleen Waugh, R David Leslie, Marian J Rewers, Aaron W Michels, Liping Yu
{"title":"针对胰岛素瘤抗原-2 （IA-2）脱酰胺细胞外表位的自身抗体与1型糖尿病的临床发病密切相关","authors":"Xiaofan Jia, Janet M Wenzlau, Caiguo Zhang, Fran Dong, Kathleen Waugh, R David Leslie, Marian J Rewers, Aaron W Michels, Liping Yu","doi":"10.2337/db24-0571","DOIUrl":null,"url":null,"abstract":"<p><strong>Article highlights: </strong>CD4+ T cells from patients with type 1 diabetes (T1D) have a significant response to post-translationally modified (PTM) deamidated IA-2 peptides; autoantibodies to these PTM neoepitopes remain to be identified in T1D. We aimed to identify autoantibodies specifically targeting reported T-cell reactive, deamidated epitopes of IA-2 and explore their relationship with T1D development. Autoantibodies to deamidated IA-2 were specific to deamidated epitopes and were predominantly present during the late stages of T1D development, challenging the hypothesis that the loss of immune tolerance occurs via post-translational modification of islet antigens. Newly identified autoantibodies to deamidated IA-2 are new biomarkers of islet autoimmunity and have the potential to aid in T1D diagnosis.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"544-553"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926269/pdf/","citationCount":"0","resultStr":"{\"title\":\"Strong Association of Autoantibodies Targeting Deamidated Extracellular Epitopes of Insulinoma Antigen-2 With Clinical Onset of Type 1 Diabetes.\",\"authors\":\"Xiaofan Jia, Janet M Wenzlau, Caiguo Zhang, Fran Dong, Kathleen Waugh, R David Leslie, Marian J Rewers, Aaron W Michels, Liping Yu\",\"doi\":\"10.2337/db24-0571\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Article highlights: </strong>CD4+ T cells from patients with type 1 diabetes (T1D) have a significant response to post-translationally modified (PTM) deamidated IA-2 peptides; autoantibodies to these PTM neoepitopes remain to be identified in T1D. We aimed to identify autoantibodies specifically targeting reported T-cell reactive, deamidated epitopes of IA-2 and explore their relationship with T1D development. Autoantibodies to deamidated IA-2 were specific to deamidated epitopes and were predominantly present during the late stages of T1D development, challenging the hypothesis that the loss of immune tolerance occurs via post-translational modification of islet antigens. Newly identified autoantibodies to deamidated IA-2 are new biomarkers of islet autoimmunity and have the potential to aid in T1D diagnosis.</p>\",\"PeriodicalId\":93977,\"journal\":{\"name\":\"Diabetes\",\"volume\":\" \",\"pages\":\"544-553\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926269/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2337/db24-0571\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2337/db24-0571","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Strong Association of Autoantibodies Targeting Deamidated Extracellular Epitopes of Insulinoma Antigen-2 With Clinical Onset of Type 1 Diabetes.
Article highlights: CD4+ T cells from patients with type 1 diabetes (T1D) have a significant response to post-translationally modified (PTM) deamidated IA-2 peptides; autoantibodies to these PTM neoepitopes remain to be identified in T1D. We aimed to identify autoantibodies specifically targeting reported T-cell reactive, deamidated epitopes of IA-2 and explore their relationship with T1D development. Autoantibodies to deamidated IA-2 were specific to deamidated epitopes and were predominantly present during the late stages of T1D development, challenging the hypothesis that the loss of immune tolerance occurs via post-translational modification of islet antigens. Newly identified autoantibodies to deamidated IA-2 are new biomarkers of islet autoimmunity and have the potential to aid in T1D diagnosis.
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