The team of academician Yan Xiyun collaborated to develop a new method for the detection of autoimmune diseases by ferritin multimeric antigen-antibody

Autoimmune diseases are chronic systemic diseases caused by the body's production of a large number of autoantibodies against autoantigens.

Therefore, the detection of specific autoantibodies in patients is the main indicator for diagnosing the disease.

For example, the detection of anti-M3 and α-fodrin antibodies in the serum of patients with primary Sjogren's syndrome (pSS) by ELISA provides an important reference for diagnosis.

However, the problem is that the sensitivity of M3 and α-fodrin peptide to detect its antibody is low, and there is a phenomenon of clinical missed diagnosis.

In order to improve the diagnostic efficiency of autoimmune diseases, the team of Yan Xiyun, an academician of the Chinese Academy of Sciences and a researcher of the Institute of Biophysics of the Chinese Academy of Sciences, and Li Zhanguo, a professor at Peking University People’s Hospital, have developed a new method based on ferritin to display multimeric antigens and multipolymers.
The new method of detecting autoantibodies by secondary antibodies increases the sensitivity of detection by 100-1000 times.

This new technology not only improves the accuracy of clinical diagnosis of pSS, but also has important significance for the diagnosis of other autoimmune diseases.

Recently, Small reported the results of this research in the form of front page illustrations.

Ferritin is a ferritin that is widely found in biological cells.
It is a core-shell structure formed by self-assembly of 24 subunits, with an outer diameter of 12nm and an inner diameter of 8nm.

In order to solve the low sensitivity of M3 and α-fodrin detection antibodies, the study uses the characteristics of the outer surface of ferritin to display polypeptides, and the antigen M3 and α-fodrin are expressed on the surface of the ferritin nanocage through gene fusion expression and polymerized to be captured.
The ability of autoantibodies is increased 10 times.

In order to further improve the sensitivity of the detection system, the research team used a similar method to display the binding peptides that recognize human antibody Fc on the surface of ferritin and label them with HRP, and designed a multimeric secondary antibody that recognizes human IgG.

This ferritin-based probe has a higher affinity for human IgG, and the sensitivity for detecting human IgG is 10 times that of traditional enzyme-labeled secondary antibodies.

Researchers combined the use of multimeric antigens that recognize patients' autoantibodies and multimeric secondary antibody probes, which can increase the sensitivity of ELISA detection of human IgG by 100-1000 times.

The results show that the capture-detection system based on ferritin nanocage is an effective detection platform and provides a new and more sensitive method for the diagnosis of autoimmune diseases.

　　The work was completed in cooperation between the Institute of Biophysics and Peking University People's Hospital.

Yan Xiyun, Fan Kelong (researcher of the Institute of Biophysics) and Li Zhanguo are the co-corresponding authors of the paper, and Zhang Yanan, a doctoral student at the Institute of Biophysics, and Li Yingni, deputy chief technician of Peking University People’s Hospital, are the co-first authors of the paper.

The research work is funded by the National Natural Science Foundation of China, the National Key Research and Development Program, the Frontier Science Key Research Program of the Chinese Academy of Sciences, the "Innovation Intersection Team" project, and the Youth Innovation Promotion Association.

Paper link: https://onlinelibrary.
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