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

Jia, Xiaofan; Wenzlau, Janet M; Zhang, Caiguo; Dong, Fran; Waugh, Kathleen; Leslie, R David; Rewers, Marian J; Michels, Aaron W et al. · Diabetes · 2025

basic_science · Level V

Where this comes from

Abstract

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.

Medical subject headings