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However, the sensitivity is often limited by the properties of the antigens and the detection systems such as enzyme\u2010linked immunosorbent assay (ELISA). Here, employing the multidisplay ability of ferritin, a highly sensitive nanocage\u2010based capture\u2010detection system is designed, of which the sensitivity is 100\u20131000\u2010fold higher than that of conventional ELISA methods. The capture nanocages are constructed by displaying the primary Sj\u00f6gren's syndrome (pSS)\u2010related antigenic peptides on ferritin nanocage, which present epitopes effectively and high affinity, leading to tenfold higher capture capability for autoantibodies. Human IgG Fc\u2010binding peptides are also engineered on ferritin nanocage, which enable high binding affinity and efficient horseradish peroxidase (HRP)\u2010labeling. Compared with commercial HRP\u2010conjugated anti\u2010human IgG antibody, the nanocage\u2010based detecting probe exhibited more than tenfold increased sensitivity. Autoantibodies are then examined in 91 sera from patients with pSS, 51 from rheumatoid arthritis, 54 from systemic lupus erythematosus, and 55 from healthy individuals by using the nanocage\u2010based ELISA. The results indicate that the nanocage\u2010based capture\u2010detection system is an effective detection platform and provide a novel and more sensitive method for the diagnosis of autoimmune diseases.<\/jats:p>","DOI":"10.1002\/smll.202101655","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T12:55:15Z","timestamp":1621860915000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nanocage\u2010Based Capture\u2010Detection System for the Clinical Diagnosis of Autoimmune Disease"],"prefix":"10.1002","volume":"17","author":[{"given":"Yanan","family":"Zhang","sequence":"first","affiliation":[{"name":"CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide Pharmaceutical Institute of Biophysics Chinese Academy of Sciences  Beijing 100101 China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingni","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Peking University People's Hospital and Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135)  Beijing 100044 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Experimental Center of Advanced Materials School of Materials Science and Engineering Beijing Institute of Technology  Beijing 100081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehui","family":"Chen","sequence":"additional","affiliation":[{"name":"CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide Pharmaceutical Institute of Biophysics Chinese Academy of Sciences  Beijing 100101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofei","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide Pharmaceutical Institute of Biophysics Chinese Academy of Sciences  Beijing 100101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoming","family":"Sun","sequence":"additional","affiliation":[{"name":"Nanjing Nanozyme Tech Co., Ltd.  Nanjing 211500 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University  Zhengzhou 450052 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelong","family":"Fan","sequence":"additional","affiliation":[{"name":"CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide Pharmaceutical Institute of Biophysics Chinese Academy of Sciences  Beijing 100101 China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 China"},{"name":"Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University  Zhengzhou 450052 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanguo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Peking University People's Hospital and Beijing Key Laboratory for 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