Cysteine carboxyethylation is an in vivo protein modification induced by the metabolite 3-HPA, which is commonly released from gut microbes. Carboxyethylated ITGA2B then induces autoantibody production and autoimmune response in AS. Our work provides a systematic workflow to identify differentially modified proteins that are important for neoantigen production in immune disorders. This approach furthers our understanding of AS pathogenesis and may aid in the development of neoantigen-based diagnosis and treatment for AS and other autoimmune diseases.

Reference
Pubmed: Zhai Y, Chen L, Zhao Q, Zheng ZH, Chen ZN, Bian H, Yang X, Lu HY, Lin P, Chen X, Chen R, Sun HY, Fan LN, Zhang K, Wang B, Sun XX, Feng Z, Zhu YM, Zhou JS, Chen SR, Zhang T, Chen SY, Chen JJ, Zhang K, Wang Y, Chang Y, Zhang R, Zhang B, Wang LJ, Li XM, He Q, Yang XM, Nan G, Xie RH, Yang L, Yang JH, Zhu P. Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity. Science. 2023 Mar 17;379(6637):eabg2482. doi: 10.1126/science.abg2482.