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

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.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.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.The drug development industry continues to invest heavily in the development of new drugs against rheumatoid arthritis (RA) based on biological regulators and antagonists of proinflammatory molecules, such as monoclonal antibodies or soluble receptor molecules. The investments are based on the expectation that biological drugs will act more specifically and with less side effects than the classical broad-acting nonbiological disease-modifying and anti-inflammatory treatments. Biological molecules have their own safety problems that are not experienced with non-biological molecules, however, such as induction of neutralizing immunity or hypersensitivity reactions caused by massive cytokine release or activation of the complement system. Owing to the high species and target molecule specificity, biological drugs are often not active in l