State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics, Beijing 102206, China.
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
J Proteome Res. 2023 Jun 2;22(6):1800-1815. doi: 10.1021/acs.jproteome.2c00799. Epub 2023 May 14.
Understanding autoimmunity to endogenous proteins is crucial in diagnosing and treating autoimmune diseases. In this work, we developed a user-friendly AAgAtlas portal (http://biokb.ncpsb.org.cn/aagatlas_portal/index.php#), which can be used to search for 8045 non-redundant autoantigens (AAgs) and 47 post-translationally modified AAgs against 1073 human diseases that are prioritized by a credential score developed by multisource evidence. Using AAgAtlas, the immunogenic properties of human AAgs was systematically elucidated according to their genetic, biophysical, cytological, expression profile, and evolutionary characteristics. The results indicated that human AAgs are evolutionally conserved in protein sequence and enriched in three hydrophilic and polar amino acid residues (K, D, and E) that are located at the protein surface. AAgs are enriched in proteins that are involved in nucleic acid binding, transferase, and the cytoskeleton. Genome, transcriptome, and proteome analyses further indicated that AAb production is associated with gene variance and abnormal protein expression related to the pathological activities of different tumors. Collectively, our data outlines the hallmarks of human AAgs that facilitate the understanding of humoral autoimmunity and the identification of biomarkers of human diseases.
了解内源性蛋白的自身免疫对于诊断和治疗自身免疫性疾病至关重要。在这项工作中，我们开发了一个用户友好的 AAgAtlas 门户（http://biokb.ncpsb.org.cn/aagatlas_portal/index.php#），该门户可用于搜索 8045 种非冗余自身抗原（AAgs）和 47 种经翻译后修饰的 AAg，这些抗原针对 1073 种人类疾病，其优先级由多源证据开发的证书评分确定。使用 AAgAtlas，根据人类 AAg 的遗传、生物物理、细胞学、表达谱和进化特征，系统地阐明了它们的免疫原性。结果表明，人类 AAg 在蛋白质序列上是进化保守的，并且在蛋白质表面富含三种亲水和极性氨基酸残基（K、D 和 E）。AAgs 富集在与核酸结合、转移酶和细胞骨架相关的蛋白质中。基因组、转录组和蛋白质组分析进一步表明，Ab 的产生与基因变异和与不同肿瘤病理活动相关的异常蛋白质表达有关。总之，我们的数据概述了人类 AAg 的特征，有助于理解体液自身免疫和鉴定人类疾病的生物标志物。
