Molecular markers of processes in cartilage in joint disease.
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Animals↗
Biomedical subjects
T Saxne
Publications and source records attributed to T Saxne.
Macromolecular markers in joint disease.
Cartilage contains a number of matrix macromolecules not present in other connective tissues. In tissue processes in disease and in normal turnover of the matrix these molecules are fragmented and released into surrounding fluids, in the case of joints into the synovial fluid. Immunoassay techniques have been developed to quantify these fragments. It appears that increased levels in synovial fluid (SF) correlate to a process in the joint cartilage. With successful therapy the level returns to normal. Interestingly, in early rheumatoid arthritis, i.e., with no discernible cartilage damage by radiography, a high SF level of one major cartilage component (proteoglycan aggrecan/fragments) is prognostic for future extensive cartilage destruction. There are major differences in the levels of proteoglycan fragments between different disease groups. Thus, patients with acute reactive arthritis have high SF levels, while patients with late rheumatoid arthritis with extensive cartilage destruction not surprisingly have subnormal values. Patients with osteoarthritis, even those with fairly extensive cartilage destruction, have elevated levels of proteoglycans/fragments in their SF, perhaps indicative of a more pronounced reparative phase.
Biomarkers↗
Immune response to collagen impregnated Dacron double velour grafts for aortic and aorto-femoral reconstructions.
This study presents 20 patients, randomised to receive either a collagen-treated or an ordinary Dacron graft for aortic reconstructions, and the results of a skin-prick test, blood parameters and ELISA for anti-collagen antibodies as well as NMR pictures during a 6 week follow-up period. Forty per cent (4/11) of those receiving a collagen impregnated graft had a significantly increased titre of antibodies and NMR revealed in two out of 11 patients either a slightly increased amount of fluid or fibrosis around the graft, both collagen impregnated. No differences were found between the graft groups concerning body temperature and leucocyte or platelet counts. The skin-prick test for collagen was negative in all cases.
Adult↗
Cytidine deaminase activity in synovial fluid of patients with rheumatoid arthritis: relation to lactoferrin, acidosis, and cartilage proteoglycan release.
It is claimed that cytidine deaminase activity reflects local granulocyte turnover or activity in the synovial fluid of patients with rheumatoid arthritis, but cytidine deaminase is not a granulocyte specific enzyme. Lactoferrin is a granulocyte specific protein that is released from the secondary granulae during activation. We measured cytidine deaminase activity and lactoferrin concentrations in 33 rheumatic synovial fluid samples. Cytidine deaminase activity and lactoferrin concentrations correlated closely, indicating that both analyses reflect similar events in the joint-that is, result in their release from granulocytes. Cytidine deaminase activity and granulocyte concentrations correlated less closely, suggesting that there are additional factors besides the cell number which contribute to this release. Joint acidosis may be one such factor, as pH and cytidine deaminase activity correlated inversely. There was no association with synovial fluid proteoglycan concentrations, a marker of cartilage degradation.
Acidosis↗
Involvement of nonarticular cartilage, as demonstrated by release of a cartilage-specific protein, in rheumatoid arthritis.
Analysis of human cartilage extracts by radioimmunoassay showed that the noncollagenous 148-kd cartilage matrix protein was present in extracts of tracheal cartilage but was undetectable in normal or arthritic joint cartilage, corroborating previous results with bovine cartilage samples. Concentrations of the protein in the circulation, as studied by radioimmunoassay, were greatly elevated in patients with rheumatoid arthritis and polyarticular juvenile rheumatoid arthritis. In contrast, patients with reactive arthritis and oligoarticular juvenile rheumatoid arthritis, as well as rheumatoid arthritis patients treated with low-dose glucocorticoids, had levels similar to those in healthy controls. The serum concentrations were not related to age. A patient with polychondritis and tracheal involvement had a high serum concentration of the protein, which decreased during plasma exchange and cyclophosphamide treatment. Studies of the release of this cartilage matrix protein, which is present in nonarticular cartilage but not in articular cartilage, should aid in the understanding of the mechanisms of cartilage involvement in disease, and the protein may become a clinically useful marker.
Aged↗
[Determination of matrix components in the synovial fluid and blood--a novel approach to studying cartilage involvement in joint disease].
Information on the structure and metabolism of a number of matrix constituents of cartilage has accumulated rapidly during the last decades. Altered dynamics of cartilage matrix in joint diseases results in increased release of macromolecules, which are now explored as potential markers of damage and severity. This article highlights some recent progress in this field with emphasis on cartilage derived proteoglycan. Disease and therapy related changes may be studied and prognostic information may be obtained by analysis of joint fluid. Future applications of this approach are promising.
Blood Chemical Analysis↗
Synovial fluid acidosis correlates with radiological joint destruction in rheumatoid arthritis knee joints.
Metabolic variables in samples of synovial fluid (SF) from 33 rheumatoid arthritis (RA) knees were analyzed. These variables were correlated with radiological destruction and SF proteoglycan concentrations. SF acidosis correlated with radiological involvement (rs = 0.62, p less than 0.002), but not with proteoglycan concentrations. A weak correlation was found between SF acidosis and granulocyte concentrations (rs = 0.37, 0.02 less than p less than 0.05). Metabolic variables covaried as expected. Samples from right and left knees from the same patients correlated regarding cellular and metabolic variables. Our results indicate insufficient nutritional supply in RA joints with increasing radiological involvement.
Acidosis↗
Cartilage derived proteoglycans in body fluids of children. Inverse correlation with age.
We have previously shown synovial fluid (SF) proteoglycan concentrations to be sensitive markers of altered cartilage metabolism in arthritis. We determined the proteoglycan concentrations in sera and SF from 23 patients with juvenile chronic arthritis and in sera from 30 healthy children by a specific enzyme linked immunosorbent assay. In both groups of children, decreasing concentrations of proteoglycans were seen during growth. Changes were most marked at the age of 12-13. The serum levels were higher in the healthy children. Our results suggest an age related metabolic change of articular cartilage, resulting in diminished release of proteoglycans to SF and blood with growing age up to 20 years. Measurement of proteoglycans could be a useful tool for studying this process.
Adolescent↗
Detection of tumor necrosis factor alpha but not tumor necrosis factor beta in rheumatoid arthritis synovial fluid and serum.
Synovial fluids from 6 of 12 patients with rheumatoid arthritis (RA) and from 3 of 11 patients with reactive arthritis contained measurable levels of tumor necrosis factor alpha (TNF alpha). Seven of 12 sera from RA patients contained TNF alpha, while only 1 of those from reactive arthritis patients was positive. Gamma-interferon was detected in the synovial fluids and sera of only the RA patients. Tumor necrosis factor beta was not detected in any sera or synovial fluids. RA patients with detectable TNF alpha had higher erythrocyte sedimentation rates and synovial fluid leukocyte counts.
Adult↗
The aminoterminal-type-III procollagen peptide and proteoglycans in serum and synovial fluid of patients with rheumatoid arthritis or reactive arthritis.
The concentrations of aminoterminal-type-III procollagen (procollagen N-) peptide, and of proteoglycans were measured in knee-joint synovial fluid and serum from patients with rheumatoid arthritis or reactive arthritis. All synovial fluids contained large amounts of intact propeptide. The synovial fluid: serum propeptide ratios were high, suggesting local propeptide liberation. A correlation was demonstrated between the propeptide concentration in synovial fluid and in serum. In rheumatoid arthritis, the propeptide concentration in synovial fluid was related to local inflammatory activity, and the serum concentration was correlated with the presence of nonspecific markers of inflammation. The presence of smaller propeptide fragments in synovial fluid indicated that some degradation occurred locally. The local metabolic changes were most prominent in patients with joint erosions. Patients with nonerosive rheumatoid arthritis and reactive arthritis had similar synovial fluid propeptide concentrations. The proteoglycan content of synovial fluid was inversely related to the degree of joint destruction, and was highest in patients with reactive arthritis. No correlation was observed between the concentrations of propeptide and proteoglycan in synovial fluid. Intraarticular glucocorticoid injection reduced the levels of propeptide and proteoglycan in synovial fluid.
Adult↗
Synovial fluid concentrations of interleukin-1 beta and proteoglycans are inversely related.
Interleukin-1 beta (IL-1 beta) and proteoglycans have been quantified by radioimmunoassay (IL-1 beta) and enzyme linked immunosorbent assay (proteoglycans) in synovial fluids and sera from patients with rheumatoid arthritis (RA) and reactive arthritis. All fluids were also tested for their ability to influence proteoglycan metabolism in a cartilage explant culture system. Synovial fluid IL-1 beta concentrations were inversely related to proteoglycan concentrations in samples from both RA and reactive arthritis patients (P less than 0.002 for all patients). There was no statistically significant relation between immunoreactive IL-1 beta concentration and proteoglycan synthesis or degradation in explants cultured in synovial fluid containing medium. Synovial fluid IL-1 beta concentrations were not related to erythrocyte sedimentation rate or joint total leukocyte count. IL-1 beta was not detectable (limit 250 pg/ml) in any unextracted sera. Although it appears likely that IL-1 beta is involved in the inflammatory and degenerative processes in joint disease, our findings indicate that there is no simple positive relationship between immunoreactive levels of this cytokine in synovial fluid and liberation of proteoglycans from articular cartilage as reflected in synovial fluid proteoglycan concentration.
Adult↗
Human arthritic synovial fluid influences proteoglycan biosynthesis and degradation in organ culture of bovine nasal cartilage.
The influence of synovial fluid and serum from patients with inflammatory joint disease on proteoglycan metabolism was studied in organ culture of bovine nasal cartilage. Proteoglycan biosynthesis, i.e. incorporation of [35S]-sulphate, was reduced after addition of synovial fluid from rheumatoid arthritis and reactive arthritis patients. Also some rheumatoid arthritis sera but no reactive arthritis serum reduced the biosynthesis compared to control sera. Proteoglycan degradation, i.e. release of proteoglycans prelabelled with [35S]-sulphate, as well as release of proteoglycans determined by chemical methods, was highest under the influence of rheumatoid arthritis synovial fluid. This effect appears to represent an activity truly stimulating degradation, since added control serum did not prevent the effect. The lowest proteoglycan degradation was observed in culture medium only. Addition of synovial fluid compared to addition of control serum did not increase proteoglycan degradation in freeze-killed cartilage indicating that the effect requires living cells. The findings are consistent with the presence in synovial fluid of mediators stimulating the chondrocytes both to activate proteoglycan degradation and to reduce proteoglycan biosynthesis.
Animals↗
Radiographic assessment in relation to clinical and biochemical variables in rheumatoid arthritis.
Radiographs of hands and feet were obtained from 125 consecutive patients with rheumatoid arthritis (RA) and the degree of destruction was assessed numerically on a 200-point scale using Larsen's standard radiographs as reference. The method is shown to possess a satisfactory degree of reproducibility. In 96 of these 125 patients, values of another 15 simultaneously determined clinical and biochemical variables were obtained. On applying linear and quadratic multiple regression analysis to this set as well as to the male and female subsets, an 'automatic' selection procedure (stepwise regression) proved duration of disease to be the most important factor relating to the 'Larsen index'. The 96 patients were therefore ranked with respect to duration of disease and divided into 4 subsets of equal magnitude. In the 3 subsets with duration of disease less than 21 years, stepwise regression produced in the final step linear or quadratic combinations not containing duration of disease but correlating quite well with the 'Larsen index' (R = 0.64-0.96). A similar result was obtained upon performing an analogous procedure in the female subset. In all instances, positive contributions of varying degree were obtained from Ritchie's index, ESR, a-antitrypsin (A1-AT), orosomucoid, fibrinogen, and IgM, while negative correlations were associated with ceruloplasmin, IgG, and IgA.
Adult↗
Measurement of synovial fluid volume using albumin dilution upon intraarticular saline injection.
A simple method for measuring synovial fluid (SF) volume is described. The degree of dilution of SF albumin after intraarticular injection of a defined volume of saline was used to calculate residual SF volume. Good correlation between calculated and aspirated SF volume was found for knee joint exudates. The method is simple, requires no radioactive tracer and should be useful in quantitative studies involving SF pathophysiology. Interestingly, the major portion of the SF could be directly aspirated, since residual volumes were small in comparison.
Adult↗
Proteoglycan concentration in synovial fluid: predictor of future cartilage destruction in rheumatoid arthritis?
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Adult↗
Cartilage proteoglycans in synovial fluid and serum in patients with inflammatory joint disease. Relation to systemic treatment.
Proteoglycan concentrations in knee joint synovial fluid and in serum from patients with various inflammatory arthritides were studied using an enzyme-linked immunosorbent assay. Patients with reactive arthritis, calcium pyrophosphate arthropathy, and juvenile rheumatoid arthritis (age less than or equal to 20 years) had the highest synovial fluid concentrations. These values differed significantly (P less than 0.001) from those in patients with rheumatoid arthritis, psoriatic arthropathy, and chronic HLA-B27-associated arthropathy. Rheumatoid arthritis patients receiving low-dose prednisolone treatment had higher synovial fluid (P = 0.006) and serum (P less than 0.001) proteoglycan concentrations than did those taking nonsteroidal antiinflammatory drugs or slow-acting antirheumatic drugs. Serum proteoglycan concentrations were near the detection limits, and did not correlate with levels found in paired samples of knee joint synovial fluid. Patients with calcium pyrophosphate arthropathy had the highest mean serum level of proteoglycan. This assay of proteoglycan antigens is a useful tool in the study of proteoglycan metabolism in patients with joint disease. With its use, differences between disease groups and effects of therapy can be distinguished.
Anti-Inflammatory Agents, Non-Steroidal↗
Cartilage proteoglycans in degenerative joint disease.
Cartilage content of proteoglycans decreases early in induced degenerative hip joint disease. Remaining molecules show structural changes indicating fragmentation. Fragments lost from the articular cartilage are released to the synovial fluid, where they can be quantified by enzyme linked immunosorbent assay. Their amounts are related to the activity of the disease process.
Animals↗
Therapeutic effects on cartilage metabolism in arthritis as measured by release of proteoglycan structures into the synovial fluid.
Proteoglycans are molecules that are degraded and released from the articular cartilage into the synovial fluid early in an arthritic process. Such released proteoglycans were quantified by an enzyme linked immunosorbent assay (ELISA). The proteoglycan content in synovial fluid from patients with various knee joint arthritides was constant in two samples withdrawn five days apart. To determine if therapeutic measures were paralleled by effects directly on the articular cartilage the patients were treated with local injections of glucocorticoids. In all patients the glucocorticoids induced a reduction of the proteoglycan content in the synovial fluid, reflecting their effects on the cartilage. In two patients with spontaneous remission of their arthritis a reduction in the proteoglycan content in the synovial fluid was also noted. The quantification of proteoglycans in synovial fluid appears to have potential as a useful tool for monitoring the effects of therapy on cartilage metabolism.
Adult↗