A R Poole

Changes in serum cartilage marker levels indicate altered cartilage metabolism in families with the osteoarthritis-related type II collagen gene COL2A1 mutation

OBJECTIVE The Arg5l9-Cys mutation in type II collagen results in severe, precocious familial osteoarthritis (OA) in 100% of carriers within the first 3 decades of life. The carrier population provided a well-defined patient population for the study of serum markers of familial OA with respect to pathogenesis, diagnosis, and prognosis. METHODS Serum was obtained from 31 mutation-positive individuals and 16 mutation-negative individuals. OA severity was determined by clinical and radiologic assessments. Levels of serum cartilage oligomeric matrix protein (COMP), keratan sulfate (KS) epitope, the 846 epitope of aggrecan, and the C propeptide of type II collagen (CPII) were measured and were correlated with the radiologic findings. RESULTS COMP and KS levels, both of which have been suggested to be indicative of disturbed cartilage turnover, were significantly elevated in mutation-positive individuals and in the individuals with OA regardless of mutation status. There was no statistically significant difference between mutation-positive, mutation-negative, OA-positive, and OA-negative individuals with respect to serum concentrations of epitope 846 or CPII, both of which are putative markers of cartilage repair. CONCLUSION Study of the macromolecular constituents of cartilage released into serum in subjects with familial OA revealed altered metabolism in OA, as demonstrated by elevated COMP and KS levels. Other constituents, the 846 epitope and CPII, were not altered, indicating dissociation of cartilage anabolism and breakdown. Future sequential studies will provide an opportunity to define biochemical changes as familial OA develops and to monitor therapeutic responses.

Cartilage proteoglycans as potential autoantigens in humans and in experimental animals.

Introduction Articular cartilage, which is an avascular tissue, is normally not subjected to surveillance by the immune system and this suggests its potential autoantigenicity. Local inflammatory processes of joints which release mononuclear cell factors (e.g., catabolin/interleukin 1) and stimulate extracellular proteinase activity may result in cartilage degradation and exposure of cartilage components as autoantigens. Thus, macromolecules peculiar to cartilage, such as type II collagen and proteoglycans, released during an active synovitis or trauma, might be recognized as foreign material and may trigger and/or maintain inflammatory diseases in patients with rheumatoid arthritis, ankylosing spondylitis and relapsing polychondritis [see references 1 and 2]. Although immunity to cartilage proteoglycans has been less extensively studied than to collagen, cartilage proteoglycans are currently considered a candidate as the cause of rheumatoid joint diseases. Immunity to injected cartilage proteoglycans can also lead to the development of inflammatory arthritis in both rabbits and dogs [3, 4] having an increased lysosomal enzyme activity. This high enzyme activity may persist for several months in the proteoglycan injected joints, and during this period severe cartilage degradation, accompanied by the production of autoantibodies, develops [5]. More evidence is