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PubMedDate not supplied

Synovial fluid in arthropathy.

The authors examined 487 synovial fluid specimens in patients affected with spontaneous effusion in the knee. In 202 of the cases the features indicating the nature of the effusion were observed (rheumatoid arthritis: 27; active S.L.E.: 2; microcrystals: 77; infections: 38; doubts as to rheumatoid arthritis or other connectivitis: 58). In 84 cases no features were determined despite the presence of specific clinical signs (psoriasis, arthrosis, previous trauma). In 201 cases where there were no clinical signs in the synovial fluid, the authors were able to differentiate moderate phlogosis in 27 specimens, and intense phlogosis in 104. Based on the results obtained, an attempt was made to define which tests are best to measure the amount of inflammation and which may be correlated with the etiology of the joint effusion.

Adolescent↗
PubMed2005

Evaluation of hyaluronidase activity in equine and bovine sera and equine synovial fluid samples by use of enzyme zymography.

OBJECTIVE: To investigate the activities of hyaluronidases in equine sera and synovial fluid samples and sera from fetal and adult bovids and evaluate the extent to which the degradation of hyaluronan is influenced by chondrocytes. SAMPLE POPULATION: Commercial and noncommercial samples of equine (n = 6) and bovine (6) sera and 16 synovial fluid samples from horses. PROCEDURE: Hyaluronidase activities in sera and synovial fluid samples were assessed via enzyme zymography (performed at pH 4, 5, 6, or 7). Chondrocytes were isolated from equine cartilage and cultured with or without hyaluronan (1 mg/mL); the degradation of hyaluronan was assessed via agarose gel electrophoresis. RESULTS: [corrected] Hyaluronidase activity was detected in equine sera and synovial fluid samples at pH 4, but not at pH 7, and in bovine sera at both pH values. In all samples at pH 4, a major band of activity (molecular weight, approx 60 kd) and some additional higher molecular weight bands were detected; high- and low-molecular-weight activities were detected in bovine sera at pH 7 Hyaluronan in tissue culture medium with or without fetal calf serum was degraded in the presence, but not the absence, of equine chondrocytes. CONCLUSIONS AND CLINICAL RELEVANCE: Hyaluronidase activity was detected in equine sera and synovial fluid at pH 4 and in bovine sera at pH 4 and 7. Primary chondrocytes in monolayer culture can degrade exogenous hyaluronan. Modulating native hyaluronidase activity may offer a new approach to improve the quantity and quality of hyaluronan in articular joints.

Animals↗
PubMedDate not supplied

Increased content of bombesin/GRP in human synovial fluid in early arthritis: different pattern compared with substance P.

OBJECTIVE: Bombesin (BN) and the mammalian homologue gastrin-releasing peptide (GRP) are known trophic factors, neurotransmitters and paracrine hormones. BN/GRP has not previously been demonstrated in synovial fluid. In this study, the amounts of BN/GRP and substance P (SP) present in synovial fluid from the knee joints of patients with rheumatoid arthritis (RA) and of healthy controls were measured. METHODS: Synovial fluid from the knee joint was collected from patients with either longstanding RA (n = 32) or early arthritis (symptoms for < 12 months; n = 9) and from control subjects, i.e., individuals without known joint disease (n = 10). These samples were analyzed using radioimmunoassays. RESULTS: Levels of BN/GRP-like peptide were below the assay detection limits in synovial fluid from controls. Detectable levels of immunoreactive BN/GRP were present in the majority of patients with either longstanding RA or early arthritis. The levels were significantly higher in the synovial fluid from patients classified as having early arthritis compared with those with longstanding RA (p < 0.05). There was a strong correlation between BN/GRP levels and the number of leukocytes in the synovial fluid in the patients with early arthritis. The levels of SP-like peptide in the patients, whether with early arthritis or longstanding RA, were significantly elevated compared with controls. However, there was no difference in the levels between these two patient groups. CONCLUSIONS: These observations show that BN/GRP-like peptide is present in the synovial fluid of joints affected by arthritis and that the pattern of BN/GRP increase differs from that of SP. It appears as if the presence of BN/GRP is particularly related to the early processes of joint involvement. These observations are of interest because BN/GRP has well-known trophic and paracrine effects and chondrocytes have recently been shown to produce neuropeptides such as BN/GRP.

Adult↗
PubMed2024

Development of methodology to support molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: The STEpUP OA consortium.

OBJECTIVES: To develop a protocol for largescale analysis of synovial fluid proteins, for the identification of biological networks associated with subtypes of osteoarthritis. METHODS: Synovial Fluid To detect molecular Endotypes by Unbiased Proteomics in Osteoarthritis (STEpUP OA) is an international consortium utilising clinical data (capturing pain, radiographic severity and demographic features) and knee synovial fluid from 17 participating cohorts. 1746 samples from 1650 individuals comprising OA, joint injury, healthy and inflammatory arthritis controls, divided into discovery (n = 1045) and replication (n = 701) datasets, were analysed by SomaScan Discovery Plex V4.1 (>7000 SOMAmers/proteins). An optimised approach to standardisation was developed. Technical confounders and batch-effects were identified and adjusted for. Poorly performing SOMAmers and samples were excluded. Variance in the data was determined by principal component (PC) analysis. RESULTS: A synovial fluid standardised protocol was optimised that had good reliability (<20% co-efficient of variation for >80% of SOMAmers in pooled samples) and overall good correlation with immunoassay. 1720 samples and >6290 SOMAmers met inclusion criteria. 48% of data variance (PC1) was strongly correlated with individual SOMAmer signal intensities, particularly with low abundance proteins (median correlation coefficient 0.70), and was enriched for nuclear and non-secreted proteins. We concluded that this component was predominantly intracellular proteins, and could be adjusted for using an 'intracellular protein score' (IPS). PC2 (7% variance) was attributable to processing batch and was batch-corrected by ComBat. Lesser effects were attributed to other technical confounders. Data visualisation revealed clustering of injury and OA cases in overlapping but distinguishable areas of high-dimensional proteomic space. CONCLUSIONS: We have developed a robust method for analysing synovial fluid protein, creating a molecular and clinical dataset of unprecedented scale to explore potential patient subtypes and the molecular pathogenesis of OA. Such methodology underpins the development of new approaches to tackle this disease which remains a huge societal challenge.

Humans↗
PubMed1993

[Clinical usefulness of rheumatoid factor in synovial fluid. Re-evaluation].

The aim of this work is to analyze the usefulness of rheumatoid factor determination in synovial fluid. One hundred twenty nine patients (29 with rheumatoid arthritis), in whom rheumatoid factor was simultaneously determined in serum and synovial fluid, were retrospectively analyzed. Serum rheumatoid factor had a 48% sensitivity, 98% specificity, 88% positive predictive value and 87% negative predictive value for the diagnosis of rheumatoid arthritis. These numbers were 76, 79, 51 and 92% respectively for synovial fluid rheumatoid factor. In rheumatoid arthritis of less than one year of evolution, serum and synovial rheumatoid factor have a sensitivity of 15% and 62% respectively, a positive predictive value of 50 and 28% respectively and a negative predictive value of 90 and 94% respectively. It is thus concluded that the absence of rheumatoid factor in serum and synovial fluid in a patient with arthritis of less than one year of evolution, renders the diagnosis of rheumatoid arthritis very unlikely. Likewise the simultaneous presence of rheumatoid factor in both fluids has a high diagnostic certainty. Among other studied variables, leukocyte count, C3 and C4 levels in synovial fluid are the best discriminators within the different diagnostic groups.

Arthritis, Rheumatoid↗
PubMed1975

[Morphological changes in the joint tissues and synovial fluid in rheumatoid arthritis and arthrosis deformans].

A simultaneous morphological investigation of bioptic material of the synovial sheath, articular cartilage, and synovial fluid from patients with various forms of rheumatoid arthritis (100 patients with a typical articular form, 10 with benign evolution, and 20 with lesions of visceral organs) was carried out. It was noted that in the usual articular form of rheumatoid arthritis the most common morphological component in the synovial sheath was lympho-plasmo-cellular infiltration. In the "benign" form of rheumatoid arthritis immunomorphological shifts were manifested but slightly, in the articular-visceral form in the immunocompetent cells there were observed karyopycnosis and plasmorrhexis. Cells and the main matter of the cartilage apparently underwent an enzymatic lysis, the intensity of which correlated with the degree of phagocytosis of the synovial fluid. In the deforming osteo-arthrosis (150 observations) in the synovial sheath there were usually noted drastic sclerosis and atrophy of organ-specific structures, impairmement of the production of the synovial fluid, and dystrophic falling into fibers of the articular cartilage with intensive proliferation of the cartilage cells. It is probable that distructiion of the cartilage in arthrosis depends upon an impairment of the function of the synovial sheath to produce synovial fluid.

Arthritis, Rheumatoid↗
PubMed1985

Plasma and synovial fluid concentrations of isoxicam in meniscectomized patients.

Concentrations of isoxicam in the plasma and synovial fluid of 7 patients were investigated by means of high-pressure liquid chromatography. The samples were collected after 7 days' treatment with a single 200 mg isoxicam capsule taken each morning. A highly significant correlation was found (r = 0.82; p less than 0.05) between isoxicam concentrations in the plasma and in the synovial fluid. The mean concentration (+/- s.d.) was 25.54 +/- 10.91 micrograms/ml in the plasma and 17.47 +/- 6.54 micrograms/ml in the synovial fluid; the ratio between isoxicam concentrations in the synovial fluid and in the plasma was 71.06% +/- 18.83.

Adult↗
PubMed1994

Role of Fc gamma receptors in the activation of neutrophils by soluble and insoluble immunoglobulin aggregates isolated from the synovial fluid of patients with rheumatoid arthritis.

OBJECTIVES: Synovial fluid from patients with rheumatoid arthritis contains both soluble and insoluble immunoglobulin aggregates which activate reactive oxidant production in human neutrophils. The objectives were to determine the roles played by Fc gamma receptors in activation of neutrophils by these complexes. METHODS: Pronase treatment was used to remove Fc gamma RIII from the neutrophil surface and blocking monoclonal antibodies were used to prevent the binding of complexes to Fc gamma RII and Fc gamma RIII. RESULTS: When Fc gamma RIII was removed from the cell surface by pronase treatment, activation by the soluble aggregates did not occur [mean (SD) inhibition 89 (16)%, n = 6] whereas activation via the insoluble aggregates was less affected [34 (16)%, n = 6]. Blocking the binding to Fc gamma RIII with antibodies decreased activation in response to the soluble aggregates [mean (SD) inhibition 71 (22)%, n = 8] but again had a lower effect on activation by the insoluble aggregates [40 (17)%, n = 9]. When binding to Fc gamma RII was blocked, activation via the soluble aggregates was substantially inhibited [mean (SD) 93 (13)%, n = 8] whereas that via the insoluble aggregates was inhibited to a much lesser extent [28 (38)%, n = 9]. When Fc gamma RII and III were simultaneously blocked, activation by the insoluble aggregates was only inhibited by 45% [(19), n = 5]. CONCLUSION: These data thus indicate that activation of human neutrophils by soluble immunoglobulin aggregates from rheumatoid synovial fluid occurs via cooperative occupancy of both Fc gamma RII and III: perturbation of binding to either of these receptor classes will abrogate activation.

Antibodies, Monoclonal↗
PubMed1982

Immunoreactive granulocyte elastase in rheumatoid synovial fluid and membrane.

A specific radioimmunoassay (RIA) was utilized to determine granulocyte elastase in the synovial fluid of a series of 45 rheumatoid joints in 39 patients. The average concentration was approximately 340 micrograms/l, exceeding that of the paired serum sample in all but 6 cases. No correlation was noted in synovial fluid between its content of granulocyte elastase and the total number of white blood cells. The concentrations in sera from rheumatoid patients with non-steroidal anti-inflammatory agents and controls were equivalent. Non-inflammatory exudates contained low concentrations of elastase. The immunoreactive granulocyte elastase in rheumatoid synovial fluid was bound to alpha 1-antitrypsin suggesting release of the enzyme in its active form. An uptake of elastase-containing complexes by macrophage-like cells in the synovial membrane was demonstrated by immunohistochemical staining of tissue using antiserum against granulocyte elastase. The concentrations of immunoreactive granulocyte elastase in the free synovial fluid of rheumatoid arthritic joints presumably only faintly reflect the situation concerning the target substrates.

Adolescent↗
PubMed1994

Local synthesis of both macrophage and T cell cytokines by synovial fluid cells from children with juvenile rheumatoid arthritis.

The production of tumour necrosis factor-alpha (TNF-alpha), TNF-beta and IL-6 in synovial fluid was studied in 50 samples of synovial fluid from 44 children with juvenile rheumatoid arthritis (JRA) by identifying cytokine production at a single-cell level. Post Ficoll-separated synovial fluid mononuclear cells were permeabilized and then intracellular TNF-alpha, TNF-beta and IL-6 protein production was examined using indirect immunofluorescence and murine anti-cytokine MoAbs. All three cytokines were measured in 37 of the 50 samples. In 25 of the 37 samples there was complete concordance; all three cytokines were present in six and absent in 19 samples. At least one cytokine was present in 27/50 (54%) of synovial fluid samples. Overall, TNF-alpha was detected in 22/49 (45%) samples, TNF-beta in 15/41 (37%) and IL-6 in 16/45 (36%) samples. Five patients had serial arthrocentesis, and in these samples there were two patients who had initially positive cytokine production, which on subsequent measurement was negative; in the other three patients there was no change from the previous cytokine production. We provide evidence that synovial fluid mononuclear cells produce monocyte and T cell cytokines in JRA. These findings suggest a role for both T cell and macrophage products in the pathogenesis of JRA, and the potential for modulation of cytokine production as a target for therapeutic intervention.

Adolescent↗
PubMed1996

Differential changes of corticotropin releasing hormone (CRH) concentrations in plasma and synovial fluids of patients with rheumatoid arthritis (RA).

Corticotropin releasing hormone (CRH) and ACTH concentrations in plasma and CRH and IL-6 concentrations in synovial fluid in patients with rheumatoid arthritis (RA) were examined to clarify the relationship between cytokines and the hypothalamic-pituitary-adrenal axis (HPA axis). Concentrations of serum amyloid A protein (SAA), one of the acute phase proteins, were also measured as an indicator of inflammation. CRH and IL-6 concentrations in synovial fluid were higher in RA patients than in control patients (osteoarthritis, OA). Plasma ACTH and CRH levels were significantly lower in RA patients than in OA patients. This suggests that CRH secretion in synovial fluid is regulated differently from plasma CRH secretion, as CRH levels in synovial fluid and plasma showed opposite changes in RA patients. SAA levels were positively correlated with the levels of CRH or IL-6 in synovial fluid, whereas there was no correlation between CRH and IL-6 levels. The results suggest that CRH and IL-6 play important independent roles in producing SAA in synovial fluid.

Adrenocorticotropic Hormone↗
PubMed1991

Diversity in antigen recognition by Mycobacterium tuberculosis-reactive T cell clones from the synovial fluid of rheumatoid arthritis patients.

In a previous study we have shown that synovial fluid mononuclear cells from many rheumatoid arthritis (RA) patients exhibit an enhanced response to M. tuberculosis antigens as compared to peripheral blood mononuclear cells. The 65-kDa heat-shock protein of M. tuberculosis was shown not to play an important role in this response, therefore other mycobacterial proteins must be involved. In this study we have investigated the possibility that synovial fluid T cells from RA patients predominantly recognize a limited number of M. tuberculosis antigens, as a result of a lesion-specific activation of only those M. tuberculosis-reactive T cells that have cross-reacted with joint-related autoantigens. From the synovial fluid of four RA patients M. tuberculosis-reactive T cell clones were isolated and analyzed for their phenotype, HLA-DR restriction and proliferation to immunoblot fractions containing sodium dodecyl sulfate-polyacrylamide gel-separated M. tuberculosis proteins of known molecular weight range. The overall M. tuberculosis immunoblot recognition pattern of the clones was strikingly heterogeneous. Within a panel of 15 clones 12 different antigenic specificities could be distinguished. In other words, we did not observe a dominant recognition of a few M. tuberculosis antigens by synovial fluid T cells. This argues against the hypothesis that the elevated synovial T cell reactivity against M. tuberculosis is a reflection of an in vivo expansion of a limited number of different types of M. tuberculosis-reactive T cells as a result of a cross-reaction with putative joint autoantigens.

Antigens, Bacterial↗
PubMedDate not supplied

[Plasminogen activator activity of the synovial fluid as an indicator of activation phenomena in degenerative joint diseases].

Activity of plasminogen activator in synovial fluids of patients with osteoarthritis was determined by a radial diffusion assay. Synovial fluid from human knee joints was obtained by joint lavage with 35 ml physiological saline containing 0.5% hydroxyethyl starch. Synovial fluids from contralateral, healthy knee joints served as controls. The activity of plasminogen activator in synovial fluid from activated (painful) osteoarthritis is significantly higher than in cases of latent osteoarthritis, whereas the activity of controls is significantly lower as in latent osteoarthritis. The findings are helpful for the discovery of patients with enhanced plasminogen activator levels in synovia which should be treated therapeutically.

Electrophoresis, Polyacrylamide Gel↗
PubMed1978

Immunodiffusion studies on synovial fluid from patients with rheumatoid arthritis: the reaction of fibrinogen with a streptococcal extract.

Synovial fluids (83.3%) from patients with rheumatoid arthritis gave a positive reaction when examined by immunodiffusion against a Lancefield extract of Group A Type 12 streptococci. None of the patients with osteoarthrosis reacted positively. An antiserum was prepared to the material in synovial fluid reacting with the streptococcal extract. This antiserum reacted positively with all synovial fluids tested including the osteoarthrosis patients. It also reacted with all plasma samples tested but only with a few (18.2%) of serum samples. Immunodiffusion and absorption experiments demonstrated that the material reacting with the streptococcal extract was fibrinogen. Of 12 other streptococci examined only one, a Group C organism, gave a similar positive reaction with synovial fluids.

Antibodies, Bacterial↗
PubMed1989

Synovial fluid changes in mycoplasma induced septicaemic polyarthritis of goat kids.

Synovial fluid samples of goat kids inoculated (ip) with 5 ml of 48 hr log phase culture of Mycoplasma mycoides sub sp. mycoides (large colony type) containing 10(7) cfu/ml were analysed for physical, cytological and biochemical properties. The synovial effusions were exudative in nature with increased volume. Gross appearances were serofibrinous, haemorrhagic and turbid containing flocculent materials with immediate clot formation. Mucinous precipitate quality was very poor having friable precipitates with cloudy supernatant. There were high total leucocytic and erythrocytic counts with significant high numbers of both neutrophils and lymphocytes. Synovial fluid sugar contents were significantly reduced, whereas total protein contents were significantly increased with concomitant reduction in albumin:globulin ratio. The alkaline phosphatase and transaminase values were also markedly increased in the synovial fluids of mycoplasma induced polyarthritic goat kids. The results may provide a clinical guideline for diagnosis, chemotherapy and prognosis of different joint diseases in domesticated animals.

Animals↗
PubMed2004

Synovial fluid leukocyte count and differential for the diagnosis of prosthetic knee infection.

PURPOSE: Criteria for the interpretation of synovial fluid are well established for native joint disorders but lacking for the evaluation of prosthetic joint failure. Our aim was to define cutoff values for synovial fluid leukocyte count and neutrophil percentage for differentiating aseptic failure and prosthetic joint infection. METHODS: We performed a prospective study of 133 patients in whom synovial fluid specimens were collected before total knee arthroplasty revision between January 1998 and December 2003. Patients with underlying inflammatory joint disease were excluded. RESULTS: Aseptic failure was diagnosed in 99 patients and prosthetic joint infection was diagnosed in 34 patients. The synovial fluid leukocyte count was significantly higher in patients with prosthetic joint infection (median, 18.9 x 10(3)/microL; range, 0.3 to 178 x 10(3)/microL) than in those with aseptic failure (median, 0.3 x 10(3)/microL; range, 0.1 to 16 x 10(3)/microL; P <0.0001); the neutrophil percentage was also significantly higher in patients with prosthetic joint infection (median [range], 92% [55% to 100%] vs. 7% [0% to 79%], P <0.0001). A leukocyte count of >1.7 x 10(3)/microL had a sensitivity of 94% and a specificity of 88% for diagnosing prosthetic joint infection; a differential of >65% neutrophils had a sensitivity of 97% and a specificity of 98%. Staphylococcus aureus was the only pathogen associated with leukocyte counts >100 x 10(3)/microL. CONCLUSION: A synovial fluid leukocyte differential of >65% neutrophils (or a leukocyte count of >1.7 x 10(3)/microL) is a sensitive and specific test for the diagnosis of prosthetic knee infection in patients without underlying inflammatory joint disease.

Adult↗
PubMedDate not supplied

Pigmented villonodular synovitis. Report of a case with diagnostic synovial fluid cytologic features.

BACKGROUND: The identification of neoplastic cells in synovial fluid is an uncommon occurrence and most often is related to extension of extraarticular tumor into the joint space than to primary neoplasm arising in the joint. CASE: In this report the cytologic features of synovial fluid obtained from the right knee of an 18-year-old male with biopsy-proven pigmented villonodular synovitis are described and compared with the features of the concurrent surgical specimen. CONCLUSION: The cytologic features of pigmented villonodular synovitis in synovial fluid include abundant mononuclear histiocytic cells occurring singly and in papillary clusters, hemosiderin within histiocytes and few multinucleated giant cells.

Adolescent↗
PubMed1997

Interleukin 1 beta and stromelysin (MMP3) activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint.

PURPOSE: This study investigated the early signs of synovitis and cartilage degradation by means of synovial fluid analysis in temporomandibular joints (TMJs) with internal derangement (closed lock) or osteoarthritis (OA). PATIENTS AND METHODS: Synovial fluid was obtained from 25 TMJs in 22 patients diagnosed with closed lock and from 15 asymptomatic TMJs of 12 normal controls. IL-1 beta concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and proteinase activity was detected by means of gelatin enzymography. RESULTS: Nine of the 25 TMJs with closed lock (CL group) exhibited osteolytic changes on the surface of the condyle. TMJs in the normal control group did not show any bony changes. Mean IL-1 beta concentration in the synovial fluid (SF) protein in the CL group was 330.1 +/- 347.7 pg per 100 micrograms protein, which was significantly higher than in the normal control (76.7 +/- 95.3 pg/100 micrograms SF-protein). Synovial fluid from the TMJs with osteolytic changes contained higher levels of IL-1 beta (531.8 +/- 379.6 pg/100 micrograms SF-protein) than those without bony changes (216.7 +/- 280.1 pg/100 micrograms SF-protein). Matrix metalloproteinase (MMP) activity with a molecular weight of 50 kd (stromelysin or MMP3) was detected in a highly augmented form in two synovial fluid samples of seven closed lock patients. CONCLUSION: The results suggest that IL-1 beta levels in synovial fluid of the TMJ have a positive correlation with OA change. The MMP3 activity detected was greatly increased in patients with cartilage degradation. These findings suggest that both changes may be important markers of early bone deterioration in TMJs that are undetectable by radiograph imaging.

Adolescent↗