Strong Association of Autoantibodies Targeting Deamidated Extracellular Epitopes of Insulinoma Antigen-2 With Clinical Onset of Type 1 Diabetes.

Diabetes Pub Date : 2025-04-01 DOI:10.2337/db24-0571
Xiaofan Jia, Janet M Wenzlau, Caiguo Zhang, Fran Dong, Kathleen Waugh, R David Leslie, Marian J Rewers, Aaron W Michels, Liping Yu
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Abstract

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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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
越来越多的证据表明,1型糖尿病(T1D)中可能逃避负选择的致病性T细胞识别自身抗原的翻译后修饰(PTM)表位。我们研究了特异性靶向胰岛素瘤抗原-2胞外结构域(IA-2ec)脱酰胺表位的自身抗体的概况,以探索它们与T1D发展的关系。我们比较了IA-2ec Q bbbbe表位(PTM IA-2ecA)和IA-2ec未修饰表位(IA-2ecA)的自身抗体在不同T1D发展阶段的参与者和其他类型的糖尿病和其他类型自身免疫个体中的特征。在新发T1D患者中,PTM IA-2ecA的患病率(26.1%)显著高于IA-2ecA的患病率(19.5%)
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