【摘要】 为了克服胶原诱导的关节炎(CIA)模型的诸如造模时间长,发病率偏低,发病严重程度较低,动物个体间疾病严重程度差异大等缺点,本试验探索采用抗Ⅱ型胶原(CII)/CD3双特异抗体联合胶原免疫来建立一个改进型CIA模型。本试验首先通过化学连接方法制备了抗CII/CD3双特异抗体。体外研究发现,该双特异抗体较好地保持了与CII以及小鼠CD3分子的结合能力,并且能同时有效地结合CII和CD3分子。体内试验发现,在胶原诱导的基础上给予抗CII/CD3双特异抗体,早在胶原免疫后25 d左右小鼠即开始发病,发病率高达100%,关节炎指数评分可以达到并稳定在10分左右的水平,并且个体间炎症严重程度差异较小。该改进型模型相对于常规CIA模型具有明显优势。该模型的成功建立,为深入揭示类风湿关节炎的发病机制、筛选和评价类风湿关节炎治疗药物,提供了更适宜的动物模型。更多还原

【Abstract】 In order to overcome the shortcomings of mouse CIA(collagen-induced arthritis) model, such as long time required for model preparation, low disease incidence, low disease severity and large variation of disease severity among individual animals. This study intends to establish an improved arthritis model induced by the anti-type II collagen(CII)/CD3 bispecific antibody(BsAb) treatment combined with the CII immunization. Firstly the anti-CII/CD3 BsAb was prepared by chemical linkage of anti-CII and anti-CD3 monoclonal antibodies. The anti-CII/CD3 BsAb maintained good binding capacities to both CII and CD3, could effectively bind these two targets simultaneously. When combined with the CII immunization, the anti-CII/CD3 BsAb resulted in early disease onset time of about 25 days after the CII immunization, 100% incidence, persistent high arthritis scores of about 10 points and low variation of disease severity among individual animals. The improved model has obvious advantages over the conventional CIA model, and it might be a new and more suitable animal model for revealing the pathogenesis of rheumatoid arthritis and, screening and evaluating for anti-rheumatoid arthritis drugs.更多还原