Collagen-Induced Arthritis

Collagen-induced arthritis (CIA) is an experimental autoimmune disease that can be elicited in susceptible strains of rodents (rat and mouse) and nonhuman primates by immunization with type II collagen (CII), the major constituent protein of articular cartilage. Following immunization, these animals develop an autoimmune-mediated polyarthritis that shares several clinical, histological, and immunological features with the human autoimmune disease rheumatoid arthritis. As with rheumatoid arthritis, susceptibility to CIA in rodents is linked to the class II molecules of the major histocompatibility complex (MHC). The immune response to CII is characterized by both the stimulation of collagen-specific T cells and the production of high titers of antibody specific for both the immunogen (heterologous CII) and the autoantigen (mouse or rat CII). Histologically, mouse and rat CIA models are characterized by an intense synovitis that corresponds precisely with the clinical onset of arthritis. Within a few days of onset, erosion of cartilage and subchondral bone by pannus-like tissue is evident, and healing by fibrosis and ankylosis of involved joints follows slowly. Because of the important similarities between CIA and rheumatoid arthritis, this experimental model of autoimmune arthritis has been the subject of extensive investigation in several laboratories.

Protocols for CIA are described for both the mouse model (see Basic Protocol 1) and the rat model (see Basic Protocol 2). In addition, protocols are included for the purification of CII from bovine articular joints and chicken sternums (see Support Protocol 1), for the purification of collagen a1(II) chains (see Support Protocol 2), and for the purification of fragments of these chains following cyanogen bromide (CNBr) digestion (see Support Protocol 3). The preparation of CII is a time-consuming procedure but is usually required because of the scarcity and expense of commercial sources of purified native CII. In addition, support protocols are provided for assessing the severity of inflammation following CIA (see Support Protocols 4, 5, and 6) and for measuring B and T cell responses to CII (see Support Protocols 7 and 8).