Serum keratan sulfate. Quantitative and qualitative comparisons in inflammatory versus noninflammatory arthritides

Mehraban, Fuad; Finegan, Candace K.; Moskowitz, Roland W.

doi:10.1002/art.1780340403

Cited by 41 publications

(18 citation statements)

References 22 publications

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“…Using antibodies to core protein and KS epitopes on aggrecan, we and others have shown that degradation products can be found in synovial fluids (SF) and sera of patients with a variety of different types of arthritis (21)(22)(23)(24)(25)(26)(27)(28)(29)(30). KS-containing fragments, measured by ELISA, have been shown to be present in increased amounts in the SF, and possibly in the serum, of patients with OA (22)(23)(24)(25), although they may be unchanged or decreased in content in the sera of patients with RA (29,30).…”

Section: Introductionmentioning

confidence: 99%

“…KS-containing fragments, measured by ELISA, have been shown to be present in increased amounts in the SF, and possibly in the serum, of patients with OA (22)(23)(24)(25), although they may be unchanged or decreased in content in the sera of patients with RA (29,30). Our previous studies using an immunoassay which detects relatively large PG fragments containing KS (31 ), revealed that there was an inverse correlation between the content of these molecules and the acute phase reactant orosomucoid in the sera of patients with RA (29).…”

Section: Introductionmentioning

confidence: 99%

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Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

Poole¹,

Ionescu²,

Swan³

et al. 1994

J. Clin. Invest.

161

112

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The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesised molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules.Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases.These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases. (J. Clin. Invest. 1994. 94:25-33.) Key words: cartilage aggrecan rheumatoid arthritis osteoarthritis

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

Poole¹,

Ionescu²,

Swan³

et al. 1994

J. Clin. Invest.

161

112

View full text Add to dashboard Cite

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“…In a variety of joint diseases, the integrity of cartilage matrix is impaired, and the degradative matrix products are released directly into the joint fluid. Although the mechanism by which cartilage metabolites emerge from the joint cavity and enter the circulation is still unclear, levels of proteoglycan fragments (2,3), KS (3,4), and the carboxy-terminal peptide of type II collagen (5) are reported to be increased in joint fluid. These molecules can usually be measured by immunochemical methods.…”

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confidence: 99%

Quantitation of chondroitin 4—sulfate and chondroitin 6—sulfate in pathologic joint fluid

Shinmei

Miyauchi

Machida

et al. 1992

Arthritis & Rheumatism

149

108

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Objective. To investigate the correlation between joint disease and the composition of chondroitin sulfate in the joint fluid, unsaturated disaccharide isomers of chondroitin 4-sulfate (.1di-4S) and chondroitin 6-sulfate (.1di·6S) were measured in joint fluids obtained from patients with osteoarthritis (OA), rheumatoid arthritis (RA), or traumatic arthritis (TA).Methods. These pathologic joint fluids were digested with chondroitinase ABC, and the .1di·4S and .1di·6S produced were determined by high performance liquid chromatography combined with fluorometry.Results. Total content of .1di-4S plus .1di·6S was 71.8 ± 30.0 nmoles/ml (mean ± SD) in OA, 55.4 ± 29.3 nmoles/ml in RA, and 211 ± 149 nmoles/ml in TA joint fluids. The ratio of .1di·6S to .1di·4S was 3.81 ± 0.992 in OA, 1.13 ± 0.527 in RA, and 5.75 ± 2.46 in TA joint fluids. Differences between groups were statistically significant.Conclusion. These results strongly suggest that the levels of chondroitin sulfate isomers and the .1di-6S: .1di·4S ratio in joint fluid reflect the proteoglycan metabolism of joint tissues, particularly of articular cartilage; hence, they could be used to diagnose joint diseases

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“…The role of KS as a biomarker of mechanical loading of the spine was reviewed by Kuiper et al, who concluded that ''the serum level of KS has the potential to be a biomarker of degeneration of intervertebral discs'' [22]. Mehraban et al, presenting the results of their study of patients with osteoarthritis and rheumatoid arthritis, also concluded that serum AgKS increases in the presence of cartilage degradation, but suggested the elevations do not quantitatively define the extent or duration of articular disorder [28]. The results of our longitudinal exploratory study of KS levels in the blood of patients with sciatica are compatible with the contention raised by Kuiper's group but this hypothesis clearly needs further testing.…”

Section: Discussionmentioning

confidence: 99%

The potential value of blood biomarkers of intervertebral disk metabolism in the follow-up of patients with sciatica

Balagué

Nordin

Schafer³

et al. 2005

Eur Spine J

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Study design: This is a prospective study with a follow-up period of 4 years. Objectives: The study aimed to evaluate the possible clinical utility of three biomarkers [i.e., keratan sulfate (KS), hyaluronan, and cartilage oligomeric matrix protein] measured in peripheral blood in severe acute sciatica at intake and follow-up. Summary of background: Our previous study and others have pointed out the interest of different laboratory tests in the acute phase of sciatica. Several blood biomarkers have been reported useful in the long-term follow-up of patients with osteoarthritis. We have found no information about the potential interest of these tests in spinal disorders. Methods: Patients were admitted to the hospital for intensive conservative management of acute sciatica (n=82). A subgroup of patients (n=33) was selected based on the duration of symptoms at visit 1, and included those with the shortest (n=24) as well as those with the longest (n=9) duration of sciatica. Blood samples were drawn, centrifuged, and the plasma frozen. Antigenic KS, hyaluronan, and cartilage oligomeric matrix protein were measured by ELISA. Patients were re-evaluated at an average of 4.3 years (range: 2.1-6.8 years). Results: Thirty-three subjects with an average age of 49.2±10.2 years participated. At intake, levels of the three biomarkers evaluated were within the range of normal values. No significant differences were found between the results of patients with a short history of sciatica ( £ 3 weeks) and those with a long duration of symptoms (>20 weeks). At follow-up, a significant increase (P<0.05) in all three biomarkers was found. Conclusions: A single measurement of these three biomarker molecules does not seem to have any diagnostic or therapeutic relevance in patients with acute radicular compression. The significance of the increase in all three biomarkers after a mean follow-up of 4.3 years is unclear; it might reflect metabolic processes involved in degenerative spinal disorders. Even though we found no correlation with clinical outcome, we believe that more research is needed.

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Serum keratan sulfate. Quantitative and qualitative comparisons in inflammatory versus noninflammatory arthritides

Cited by 41 publications

References 22 publications

Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

Quantitation of chondroitin 4—sulfate and chondroitin 6—sulfate in pathologic joint fluid

The potential value of blood biomarkers of intervertebral disk metabolism in the follow-up of patients with sciatica

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