Collagen-induced arthritis in common marmosets: A new nonhuman primate model for chronic arthritis

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.

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