Jia Xiaofan, Wenzlau Janet M, Zhang Caiguo, Dong Fran, Waugh Kathleen, Leslie R David, Rewers Marian J, Michels Aaron W, Yu Liping
Barbara Davis Center for Diabetes, University of Colorado, Aurora, CO.
Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, U.K.
Diabetes. 2025 Apr 1;74(4):544-553. doi: 10.2337/db24-0571.
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.
1型糖尿病（T1D）患者的CD4 + T细胞对翻译后修饰（PTM）的脱酰胺化IA-2肽有显著反应；针对这些PTM新表位的自身抗体在T1D中仍有待确定。我们旨在鉴定特异性靶向已报道的IA-2 T细胞反应性脱酰胺化表位的自身抗体，并探讨它们与T1D发生发展的关系。针对脱酰胺化IA-2的自身抗体对脱酰胺化表位具有特异性，并且主要出现在T1D发展的后期，这对免疫耐受丧失是通过胰岛抗原的翻译后修饰发生的假说提出了挑战。新鉴定的针对脱酰胺化IA-2的自身抗体是胰岛自身免疫的新生物标志物，有可能有助于T1D的诊断。
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