Age-related changes in the antigenicity of human articular cartilage proteoglycans

Rabbits were immunized with adult or foetal human articular cartilage proteoglycans and cell-mediated and antibody immunity assessed in vitro. Cellular immunity to proteoglycans of different ages was measured by the stimulation of 3H-thymidine incorporation into cultured spleen cells. Antibodies to proteoglycans in the rabbit sera were detected with an enzyme-linked immunosorbent assay. The ability of adult and foetal proteoglycans to preabsorb antibody activity in this assay was compared. The results from both the cellular and antibody studies support the same conclusion, that adult proteoglycans express all foetal antigenic determinants and have additional determinants not seen on foetal proteoglycans. The reactivity of rabbit spleen cells to proteoglycans of different ages indicated that these determinants appear during maturation when the major changes in proteoglycan structure occur. The results did not appear to be due to differences in chondroitin sulphate content of the preparations, since the same observations were made with chondroitinase ABC-digested proteoglycans. The observations might be explained by other differences in glycosylation between the preparations or by postulating the synthesis during maturation of an additional proteoglycan species with a different core-protein. Such changes in the antigenicity of articular cartilage proteoglycans with age could account for the development of autoimmunity to proteoglycans in inflammatory joint diseases and may play a role in their pathogenesis.