Study on immunogenicity and arthritogenicity of a synthetic cyclic citrullina-ted peptide / 中国免疫学杂志

ABSTRACT

Objective:To establish a synthetic cyclic citrullinated peptide induced arthritis model in mice, explore immunogenicity and arthritogenicity of this peptide. Methods: 36 DBA/1 mice were randomly divided into three groups, which were injected the type Ⅱ collagen ( CⅡ, CIA ) emulsion, cyclic citrullinated vimentin peptide ( CCit-Vim, CCV-IA ) emulsion, cyclic citrullinated vimentin peptide conjugated KLH ( CCit-Vim+KLH,CCV+K-IA) emulsion on day 0 and 21,respectively. Using arthritis index( AI) ,paw swelling to evaluate the incidence of arthritis;ELISA tested serum anti-CCit-Vim antibody,anti-CⅡantibody,anti-CCP antibody and TNF-α, IIF detected AKA;Histopathology of the ankle joint was obsearved. Results: There were three mice appeared arthritis in CCV+K-IA,the incidence rate of 25%,but arthritis occurs later time,short duration,and the incidence and extent of arthritis were lower than the CIA. CCV-IA no arthritis performance. CCV+K-IA produce anti-CCit-Vim antibody were significantly higher than those in CIA (1. 32±0. 59 vs 0. 78±0. 27,P=0. 031). While Anti-CCP antibody of CCV+K-IA were significantly lower than CIA (54. 73±7. 33 vs 64. 37±9. 91,P=0. 007). The anti-CⅡ antibody in CCV+K-IA and CCV-IA were lower than the CIA(15. 73±2. 10, 16. 71±3. 03 vs 19. 50±2. 36,P<0. 05). The TNF-α produced by CCV+K-IA and CIA were both significantly higher than the CCV-IA (645. 61±35. 26,618. 98±53. 32 vs 533. 63±79. 49,P<0. 05). The AKA positive rate of CCV+K-IA is 50% (6/12),significantly higher than CCV-IA 25% ( 3/12 ) and CIA 16. 67% ( 2/12 ) . Histopathology of the ankle showed that the CCV-IA and CCV+K-IA have a mild synovial hyperplasia,no obvious synovial pannus formation and inflammatory cell infiltration. Conclusion:The cyclic citrul-linated peptide conjugated KLH not only has stronger immunogenicity but also has arthritogenicity. It induced a higher positive rate of AKA than CⅡ.