Inflammation and cartilage metabolism in rheumatoid arthritis. Studies of the Blood Markers Hyaluronic Acid, Orosomucoid, and Keratan Sulfate

Abstract

Single analyses of peripheral blood of rheumatoid arthritis (RA) patients showed a significant reduction in the mean value for keratan sulfate (KS) compared with that in control subjects, but the mean value for orosomucoid (OM) was elevated compared with that in control subjects. Some RA patients displayed highly elevated levels of hyaluronic acid (HA), while others exhibited normal levels. There was a significant inverse correlation between OM and KS content in RA patients, as well as a direct correlation between HA and OM. In longitudinal studies of RA patients, parallel changes in OM and HA and inverse changes between KS and OM or HA were commonly observed. Clinical analyses revealed that there was an inverse correlation between KS and morning stiffness, and direct correlations between the number of tender joints and HA, and between HA or the erythrocyte sedimentation rate and the number of joints with effusions. The reason(s) for the inverse correlation between KS and OM as an index of systemic inflammation remains to be established. Circulating HA represents an index of joint inflammation, for which a marker has not been previously available.

Serum hyaluronan levels increase with the total number of osteoarthritic joints and are strongly associated with the presence of knee and finger osteoarthritis

“…Our study suggests that serum HA values are affected by the presence of involved OA joints in multiple sites in individuals without other serum-HA-related factors. This biomarker increases in the presence of articular synovitis and cartilage damage [6,7]. Inflamed synovium produces more HA locally and secretes it into the synovial fluid [20].…”

“…There are many biomarkers for cartilage, bone and synovitis [5]. Among them, serum hyaluronan (HA) level is considered a good biomarker for reflecting cartilage damage and synovitis in OA patients [6,7]. Previous studies show its association with the presence [7][8][9], duration [10] and severity of radiographic OA [11]; degree of pain [5,11,12]; and OA progression [13].…”

Serum hyaluronate level as a predictor of radiologic progression in early rheumatoid arthritis

“…The finding that the levels of HA in the RA patients we studied were not as high as those in other RA patient groups (43) may reflect the fact that all of our patients had early disease, and thus had less inflamed synovial tissue mass than would be found in patients with more advanced RA. Elevated concentrations of HA in the serum of RA patients appear to be related to acceler- ated production of HA in inflamed joints, and the resultant increase in the amount of degradation products appearing in the serum (17)(18)(19)(20). Monokines, especially tumor necrosis factor CY and interleukin-1 a, which are detected in increased quantities in the joints of RA patients (21,22), stimulate HA production by synovial fibroblast-like cells (23).…”

Circulating and synovial fluid hyaluronan levels

“…Prior to IA steroid injection, the albumin removal rate was significantly lower in OA than in RA patients (P = 0.005). Changes in albumin clearance were not significantly influenced by IA steroids in the AS patients, although there were decreases in the V, at 50-80 days post-IA steroid (P = 0.025), with the rates of albumin removal ranging from 2.01 to 6.00.…”

“…In contrast, the HA concentration in serum from RA patients is markedly increased (5-8). It has been suggested that these increases may be the result of synovitis (5,6,9) and associated alterations in the rate of HA clearance from RA joints. However, the relationship between the structural and physiological changes that occur during inflammation and the distribution of HA remain poorly understood.…”