MAPPING OF ARTHRITOGENIC AUTOIMMUNE EPITOPES OF CARTILAGE AGGRECANS IN PROTEOGLYCAN-INDUCED ARTHRITIS

Immunization of BALB/c mice with chondroitin sulfate-depleted proteogl ycan (aggrecan) of fetal human cartilage produces progressive polyarth ritis and ankylosing spondylitis. The development of the disease in ge netically susceptible BALB/c mice is dependent upon the expression of both cell-mediated and humoral immune responses against the host mouse cartilage proteoglycan (PG). Although cartilage PGs from various spec ies have many biochemical and immunological similarities, only a selec t group of PGs from fetal and newborn human, fetal pig and canine arti cular cartilages, human osteophytes and human chondrosarcomas are able to induce arthritis in BALB/c mice. Arthritis develops only in mice t hat also develop autoantibodies to self-cartilage PGs, although autoan tibodies occasionally are present in non-arthritic animals as well. Th e protease-sensitive auto/arthritogenic epitope(s) is located in, or c lose to, the chondroitin sulfate (CS) attachment region of the PG mole cule. The primary structure of the core protein is responsible for the autoimmune/arthritogenic effect of this select group of PGs, whereas the core protein epitopes are masked by glycosaminoglycan (GAG)-side c hains. The CS side chains seem to inhibit antigen recognition in all a ggrecans with arthritogenic potential, whereas a similar effect with k eratan sulfate (KS) appears only in PGs of aging cartilages.