Alhamar Ghadeer, Vinci Chiara, Franzese Valentina, Tramontana Flavia, Le Goux Nelig, Ludvigsson Johnny, Nissim Ahuva, Strollo Rocky
Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait.
Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium.
Front Immunol. 2025 Feb 14;16:1537405. doi: 10.3389/fimmu.2025.1537405. eCollection 2025.
The pathogenesis of type 1 diabetes (T1D) involves a complex interplay of genetic predisposition, immune processes, and environmental factors, leading to the selective destruction of pancreatic beta-cells by the immune system. Emerging evidence suggests that intrinsic beta-cell factors, including oxidative stress and post-translational modifications (PTM) of beta-cell antigens, may also contribute to their immunogenicity, shedding new light on the multifaceted pathogenesis of T1D. Over the past 30 years, neoepitopes generated by PTMs have been hypothesized to play a role in T1D pathogenesis, but their involvement has only been systematically investigated in recent years. In this review, we explored the interplay between oxidative PTMs, neoepitopes, and T1D, highlighting oxidative stress as a pivotal factor in immune system dysfunction, beta-cell vulnerability, and disease onset.
1型糖尿病（T1D）的发病机制涉及遗传易感性、免疫过程和环境因素之间的复杂相互作用，导致免疫系统选择性破坏胰腺β细胞。新出现的证据表明，内在的β细胞因子，包括氧化应激和β细胞抗原的翻译后修饰（PTM），也可能导致其免疫原性，为T1D多方面的发病机制提供了新的线索。在过去30年中，PTM产生的新表位被认为在T1D发病机制中起作用，但直到近年来才对其参与情况进行系统研究。在本综述中，我们探讨了氧化PTM、新表位和T1D之间的相互作用，强调氧化应激是免疫系统功能障碍、β细胞易损性和疾病发生的关键因素。
