Proteoglycan‐induced arthritis in balb/c mice

Abstract

Immunization with chondroitinase ABC-digested fetal human cartilage proteoglycan and Freund's complete adjuvant induced polyarthritis and ankylosing spondylitis in female BALB/c mice. The initial external symptoms of the joint inflammation were swelling and redness. This was associated with edema of the synovium and periarticular tissues and gross proliferation of cells, which reached a peak during weeks 7-9 of the experiment. Mononuclear cell infiltration, with perivascular concentration and occlusion of small vessels, was common. Synovitis increased in severity, villous pannus developed, and erosions of bone, articular cartilage, and occasionally, growth plate were observed. The lumbar spine and the proximal intervertebral discs of the tail also exhibited inflammatory and degenerative changes. As the arthritis progressed, sometimes with acute in- flammatory exacerbations, more joints became involved and, by the sixteenth to the twentieth weeks of the experiment, a progressive polyarthritis, with gross joint deformities and restricted function, developed in the majority of the limb joints. Clinical and morphologic features of the disease correlated well with radiologic analysis and with an increased deposition of wmT~-methylene diphosphonate (determined by radionuclide imaging). The development of this arthritis was accompanied by the expression of cell-mediated and humoral immunity to the immunizing antigen. However, this immunity was also observed, although it was generally less well developed, in mice that received the intact or digested proteoglycan without adjuvant. These mice did not usually develop arthritis. Control mice that received only adjuvant did not develop arthritis.Inflammatory arthritis, with destruction and erosion of articular cartilage, is associated with the development of autoimmunity to type I1 cartilage collagen (1-8) and to cartilage proteoglycan (3)(4)(5)(9)(10)(11)(12), and this may be related to the immunopathology of the disease. The immunity expresses itself through both the production of autoantibodies and the development of T cell-mediated cellular immunity. Whereas in rheumatoid arthritis, immunity is often directed against type I1 cartilage collagen (7,13,14)-particularly to its degraded form (2-5)-i n ankylosing spondylitis, immunity to cartilage proteoglycan has been detected more frequently (3,9).Destruction of articular cartilage in experimentally induced synovitis (8,(15)(16)(17) and osteoarthritis (18) also results in the development of cellular immmity to cartilage collagen and proteoglycan. Injection of

Immunity to cartilage proteoglycans in balb/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan

“…We have reported that female BALBk mice that have been immunized with fetal human proteoglycan in adjuvant develop progressive polyarthritis with ankylosing spondylitis (22). Clinical studies, including radiographic analyses and scintigraphic bone scans, together with the histopathologic study of diarthrodial joints and spine, showed many similarities to both rheumatoid arthritis and ankylosing spondylitis.…”

“…The arthritis starts as a polyarticular synovitis, including a spondylitis, which becomes progressive and produces cartilage and bone erosion within the joint, with stiffness and deformities in diarthrodial joints, resorption of growth plates and intervertebral discs, and ankylo- * Fetal human proteoglycan (PG) monomer digested with chondroitinase ABC (chase ABC) was used to determine the antibody concentration, by solid-phase radioimmunoassay, on day 28 of immunization, and to determine the stimulation index during weeks 16-20 of immunization. Data from groups 1-13 have been presented in part elsewhere (22). All mice were female, except for those in group 9, which were male.…”

“…Proteoglycans treated with glycosidases were purified on a Sephacryl S-200 column (82 x 2.6 cm) in the presence of 4M guanidinium chloride. The purity of the antigen was determined as previously described (22). Analytical methods, such as determination of uronic acid, sialic acid, hexosamine, and protein content, have also been described (23,24).…”

“…All mice were examined daily to record clinical changes, which were documented as described previously (22). Limbs, tails, and lumbar spines were fixed, sectioned, and stained for histopathologic assessment as described (22).…”

Cartilage oligomeric matrix protein (COMP)-induced arthritis in rats

“…bovine, proteins [8][9][10]. The major proteoglycan of the joint, aggrecan, has also been shown to induce arthritis in certain mouse strains, if given in a heterologous (human) form [11]. The induction of arthritis with heterologous cartilage proteins may be a way to circumvent the strong tolerance of T cells specific for cartilage proteins [12].…”