2022, Vol. 26 ›› Issue (18): 2930-2937

Research progress of rheumatoid arthritis animal model with high expression of anti-citrullinated protein antibodies

Yang Chao1, Zhong Gejia2, Liu Chunfang1, Lin Na1   

Abstract: BACKGROUND: Anti-citrullinated protein antibody is a specific and early diagnostic marker of rheumatoid arthritis, which is closely related to the occurrence and development of rheumatoid arthritis and the aggravation of bone destruction. The condition of patients with positive antibodies of this type is more serious and more difficult to treat than patients with negative antibodies. Collagen-induced arthritis and adjuvant-induced arthritis are two typical rheumatoid arthritis animal models, but they do not express or stably express anti-citrullinated protein antibody at a high level, which seriously affects the in-depth research regarding pathogenesis of anti-citrullinated protein antibody-positive rheumatoid arthritis and therapeutic drugs.   
OBJECTIVE: To consult relevant domestic and foreign literature, to comprehensively analyze the current research status of the rheumatoid arthritis animal model with high anti-citrullinated protein antibody expression through the existing literature, to point out the existing problems, and to put forward research recommendations.
METHODS:   Using “Rheumatoid Arthritis, ACPA” or “Rheumatoid Arthritis, anti-CCP” as English search terms, and “Rheumatoid Arthritis, anti-citrullinated protein antibody” as Chinese search terms, PubMed, Web of Science, CNKI, Wanfang, and VIP databases were searched for articles published before August 2021. Finally, 61 articles were included.   
RESULTS AND CONCLUSION: (1) The methods for establishing rheumatoid arthritis animal models with high anti-citrullinated protein antibody expression include anti-citrullinated protein antibody monoclonal antibody induction, citrullinated protein induction, Porphyromonas gingivalis induction and other methods. Different modeling methods have their own characteristics. (2) The citrullinated protein induction model has the most reports and the most obvious features of arthritis. This type of protein is one of the target antigens for the onset of rheumatoid arthritis and can well simulate the pathological changes of the human body. It is the preferred model for establishment. (3) Citrullinated protein induction is the same as the anti-citrullinated protein antibody monoclonal antibody induction method. The preparation of the modeling agent is cumbersome and difficult to obtain. (4) The Porphyromonas gingivalis induction model has low economic cost and relatively simple and easy modeling materials. However, it will be combined with periodontitis and other complications. (5) Taken together, future research is to find suitable anti-citrullinated protein antibody monoclonal antibodies, citrullinated protein or short peptides as immune inducers, and select animals with genetic background and immunological factors that are suitable for the onset of human rheumatoid arthritis, and explore the rational use of Porphyromonas gingivalis, optimize the modeling conditions, and hope to establish an animal model that can reflect the entire process of human anti-citrullinated protein antibody-positive rheumatoid arthritis. This is an urgent task in the field of rheumatoid arthritis research in the future.
Key words: model, animal, anti-citrullinated protein antibody, high expression, rheumatoid arthritis, Porphyromonas gingivalis, gingiva, monoclonal antibody, protein