Study On The Rhesus Monkeys’ Model Of Rheumatoid Arthritis Induced By A Synthetic Cyclic Citrullinated Peptide

BackgroundRheumatoid arthritis（RA）is one of the most common chronic systemic autoimmune diseases characterized by erosive arthritis.Its important pathological features,chronic synovitis and pannus formation of synovium often cause progressive destruction of the affected joints,leading to a high disability rate.In recent years,a large number of basic and clinical studies have revealed that citrullinated proteins and their specific antibodies play an important role in the initiation and maintenance of immune inflammation in RA.Citrullinated proteins have attracted extensive attention as a possible initiating antigen of RA.However,the question of when,where and how citrulline proteins break immune tolerance and trigger immune response remains unclear.Some rheumatoid arthritis rat models induced by citrulline protein are different from human RA in the location and pathological characteristics of arthritis,and the small joint structure of rodent models limits the application of X-ray and joint ultrasonography in monitoring model arthritis.Therefore,the research and development of high purity citrullinated protein short peptide induced RA model in rhesus monkeys for imaging and pathological correspondence study is of great significance not only to explore the exact role of citrullinated protein in the pathogenesis of RA,but also to image examination in the diagnosis and prediction of RA.ContentObjectiveTo establish a new arthritis model in rhesus monkeys induced by synthetic cyclic citrullinated peptide,and compared with the type Ⅱ collagen-induced arthritis model from the aspects of arthritis signs,imaging,immunology response and histopathology.Methods8 rhesus monkeys were randomly divided into two groupsand immunized with collagen type Ⅱ（C Ⅱ,CIA）and cyclic citrullinated peptide（CCit-Vim+KLH,CCV+K-IA）coupled with hemocyanin（KLH）respectively.The signs and inflammation indexes of macaques were observed continuously.The imaging examination of the joints of the extremities（X-ray,joint B-ultrasound）was performed at the 4th week and the 8th week.The joint histopathological examination was performed after the 12th week.ResultsThe incidence of rhesus monkey arthritis in CCV+K-IA and CIA was 3/4 and 4/4.Arthritis in CCV+K-IA group appeared at the 6th week after immunization.The severity and location of arthritis were the same as CIA.The levels of anti-CCit-Vim and IL-6 in CCV+K-IA were higher than those in CIA（P=0.0315;P=0.0335）,but there was no significant difference in the levels of anti-CCP antibody,anti-CⅡantibody and TNF-alpha（P>0.05）.The results showed that there was no significant difference between CCV+K-IA and CIA in X-ray Sharp score,joint ultrasound synovitis and pathological synovitis semi-quantitative score.ConclusionThe cyclic citrullinated peptide conjugated KLH can induces arthritis in rhesus monkeys and induces higher levels of anti-CCit-Vim antibodies than CIA.