Collagen-induced arthritis in common marmosets: a new nonhuman primate model for chronic arthritis
Collagen-induced arthritis in common marmosets: a new nonhuman primate model for chronic arthritis
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DOI：
10.1186/ar3172
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发表时间：
2010-01-01
影响因子：
4.9
通讯作者：
't Hart, Bert A.
中科院分区：
文献类型：
--
作者：
Vierboom, Michel P. M.;Breedveld, Elia;'t Hart, Bert A.
前言：在类风湿性关节炎(RA)领域，越来越需要动物模型来评估新疗法的有效性和安全性。特别是对于针对疾病进展阶段的人类特异性生物制剂的早期临床前评估，需要相关的动物模型。根据这一要求，我们着手建立了一种小型非人灵长类动物(成年时体重为300~400g)的胶原诱导性关节炎(CIA)模型，即普通绒猴(Callithrix Jacchus)。方法：将22只动物分为3个实验，分别用不同免疫策略的牛源和鸡源II型胶原(CII)免疫动物。分析关节炎的临床表现、血液学和临床化学、抗CII的免疫学反应和关节炎的组织病理学特征。结果：几乎100%(21/22)的动物出现了临床明显的关节炎。50%的动物发展为半急性CIA，而另外50%的动物表现为更慢性的疾病。CII的细胞免疫应答(CD3/CD4和CD3/CD8)和体液免疫应答(IgM和Ig G)均参与了该病的发生发展。结论：与猕猴单相、破坏性CIA模型相比，该模型在慢性病程和病理形态上更接近于慢性RA。因此，该模型可以填补新的人类特定疗法的临床前测试的空白。
Introduction: There is an ever-increasing need for animal models to evaluate efficacy and safety of new therapeutics in the field of rheumatoid arthritis (RA). Particularly for the early preclinical evaluation of human-specific biologicals targeting the progressive phase of the disease, there is a need for relevant animal models. In response to this requirement we set out to develop a model of collagen-induced arthritis (CIA) in a small-sized nonhuman primate species (300 to 400 g at adult age); that is, the common marmoset (Callithrix jacchus).Methods: Twenty-two animals divided into three experiments were immunized with collagen type II (CII) of either bovine or chicken origin with different immunization strategies. The animals were analyzed for clinical manifestation of arthritis, hematology and clinical chemistry, immunological responses against CII and histopathological features of the arthritis.Results: Clinically manifest arthritis was observed in almost 100% (21 out of 22) of the animals. Fifty percent of the animals developed semi-acute CIA while the other 50% displayed a more chronic disease. Both cellular (CD3/CD4 and CD3/CD8) and humoral responses (IgM and IgG) against CII were involved in the development of the disease. Besides mild histopathological changes in bone and cartilage, severe inflammation in extraarticular tissues like periosteum and subcutaneous tissues was observed.Conclusions: This new model in marmosets more closely resembles chronic RA with respect to the chronic disease course and pathomorphological presentation than the more acute monophasic and destructive CIA model in macaques. This model can therefore fill a niche in preclinical testing of new human specific therapeutics.