Post‐translationally modified neoantigens: Promising targets for diagnostic strategy of autoimmune diseases

作者：Yue Zhai, Ping Zhu · 发表于：Clinical and Translational Medicine · 年份：2023 · DOI：10.1002/ctm2.1373 · 被引用次数：11 · 研究领域：T-cell and B-cell Immunology、Cytokine Signaling Pathways and Interactions、Monoclonal and Polyclonal Antibodies Research

Autoimmune diseases can be caused by emerging neoantigens that break immune tolerance in humans. With increasing prevalence of autoimmune diseases, the key understanding of emerging neoantigens and most importantly the related-diagnosis are urgently needed.1 The development of etiological diagnosis of autoimmune diseases is of great significance for disease targeted therapy. As major histocompatibility complex (MHC) subtypes of patients are highly related to autoimmune disease, identifying newly appearing self-antigens that interact with MHC and induce adaptive immune responses is vital. Post-translational modifications (PTMs) such as phosphorylation, methylation and acetylation are known for their biological functions important for signal transduction and transcription regulation. PTMs have also been shown to produce self-generated neoantigens from existing proteins and peptides by altering the primary structure of proteins, that is, by altering the protein ‘self’ sequence, without the need to introduce antigens from microbial and somatic mutations. One of possible source of PTM neoantigen is the changes of metabolites. The generation of metabolic PTM-related neoantigens in autoimmune diseases may be one of the main causes of disease and provide strategies for the systematic diagnosis and evaluation. For chronic autoimmune diseases such as ankylosing spondylitis (AS), 3-hydroxypropionic acid (3-HPA) induces cysteine carboxyethylated neoantigen, promotes antigen-specific CD4 ...