Zhai Yue, Wu Kefei, Lin Qi, Cao Zhenzhen, Jia Yankun, Zhu Ping
Department of Clinical Immunology, Xijing Hospital, and Department of Cell Biology of National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, Shaanxi, 710032, China.
Adv Sci (Weinh). 2025 Sep;12(34):e01766. doi: 10.1002/advs.202501766. Epub 2025 Jun 19.
Autoimmune diseases, like spondyloarthritis (SpA) and rheumatoid arthritis (RA), have a high incidence and disability rate and are major diseases that seriously endanger human health. The pathogenesis of autoimmune diseases involves the interaction among genetic factors, environmental factors, and immune disorders. The post-translational modified neoantigens are the key nodal of these three factors. Under the intervention of the external environment, changes in metabolic status in vivo induce metabolite-related post-translational modifications (PTMs). These PTM proteins and peptides, after being presented by human leukocyte antigen (HLA) molecules of specific genotypes, can trigger autoreactive T cell expansions which are antigen-specific and then develop into autoimmunity. Such biological processes are a great challenge to the immune tolerance status and can be an important cause of autoimmune diseases.
自身免疫性疾病，如脊柱关节炎（SpA）和类风湿关节炎（RA），发病率和致残率都很高，是严重危害人类健康的主要疾病。自身免疫性疾病的发病机制涉及遗传因素、环境因素和免疫紊乱之间的相互作用。翻译后修饰的新抗原是这三个因素的关键节点。在外部环境的干预下，体内代谢状态的变化会诱导与代谢物相关的翻译后修饰（PTM）。这些PTM蛋白和肽在特定基因型的人类白细胞抗原（HLA）分子呈递后，可触发抗原特异性的自身反应性T细胞扩增，进而发展为自身免疫。这样的生物学过程对免疫耐受状态是一个巨大挑战，可能是自身免疫性疾病的重要病因。
