Cryptic T-cell epitopes and their role in the pathogenesis of autoimmune diseases.

Immune recognition of self-proteins features prominently in the early pathogenesis of autoimmune rheumatic diseases such as rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and systemic sclerosis. The mechanisms which provide lymphocytes with access to such autoantigens are therefore fundamental in creating the opportunity for autoimmune responses to develop. It has long been thought that the tissue or cellular location of some self-proteins may determine that they are normally 'hidden' from immune recognition, thereby reducing their potential for autoantigenicity. Recently, this concept has been extended to apply even to different epitopes within the same protein. Many studies, encompassing a wide variety of antigens, have shown that some epitopes are not presented for recognition by T lymphocytes unless they are produced in unusually large concentrations or unless they are freed from the configuration of their native antigen. Epitopes for which this phenomenon occurs are described as cryptic. There is increasing interest in the possibility that crypticity may be an important characteristic of epitopes which are recognized by T lymphocytes in autoimmune pathogenesis. The evidence which has led to this theory and its significance are reviewed.

Alteration of cartilage metabolism by cells from osteoarthritic bone.

OBJECTIVE: To determine whether bone cells alter cartilage metabolism. METHODS: Bone cell cultures were established using explants obtained from the hip and knee joints of 9 patients with osteoarthritis (OA) and 6 subjects without arthritis (nonarthritic [NA]). NA human cartilage biopsy samples were incubated in the presence or absence of bone-derived cells, and the effects on glycosaminoglycan (GAG) release from cartilage were measured. RESULTS: Bone cell cultures secreted osteocalcin (OC) and did not contain cells expressing leukocyte common antigen. None of the 8 cultures established from NA bone, compared with 17 of 32 from OA bone, significantly altered GAG release from cartilage (P = 0.006). In knees with medial joint damage, 38% of the cultures derived from the medial side of the joint increased GAG release from cartilage. In contrast, 77% of the cultures derived from the lateral side of the joint had an effect on GAG, with 38% increasing and 38% decreasing GAG release. Seven cytokines were measured in OA bone cell supernatants. No significant difference was apparent in the concentration of any one cytokine when supernatants were compared according to their effects on GAG release. CONCLUSION: Bone cells from OA patients can influence cartilage metabolism. This might explain why increased subchondral bone activity can predict cartilage loss.