Yersinia specific immune complexes in the synovial fluid of patients with yersinia triggered reactive arthritis.

Yersinia specific immune complexes were demonstrated in the synovial fluid of three patients out of 12 with yersinia triggered reactive arthritis. They were not detectable in the synovial fluid of any of the 16 control patients, including nine with reactive arthritis triggered by factors other than yersiniae. Platelet reactive IgG was detectable in the synovial fluid of eight out of the 12 patients with yersinia triggered reactive arthritis and in three of the 16 control patients, all three having rheumatoid arthritis. An enzyme linked immunosorbent assay and a platelet 125I labelled staphylococcal protein A test were used to measure yersinia specific immune complexes and platelet reactive IgG respectively. The results obtained show for the first time the occurrence of bacterial antigens, derived from the causative strain, in the synovial fluid in yersinia triggered reactive arthritis.     

Isolation of Yersinia-specific T cell clones from the synovial membrane and synovial fluid of a patient with reactive arthritis.

Synovial fluid (SF) mononuclear cells from patients with reactive arthritis (ReA) proliferate in vitro when challenged with ReA-associated bacteria, the maximal response being for the organism causing the triggering infection. We report the results of a study of the antigenic specificity of synovial T lymphocytes from an HLA-B27 positive ReA patient whose SF mononuclear cells responded preferentially to Yersinia antigens. This is the first report of the isolation of Yersinia-specific T cell clones from synovial membrane (obtained by closed-needle synovial biopsy). We present a detailed analysis of these clones, together with others obtained from the SF.     

Increased serum and synovial fluid antibodies to immunoselected peptides in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the role of potential immunoselected phages displaying random peptides in addition to possible antigen leads in rheumatoid arthritis (RA) by assaying the levels of synovial fluid (SF) and serum antibodies to synthetic peptides. METHODS: Serum and SF antibodies from patients and controls were measured using an enzyme linked immunosorbent assay (ELISA). RESULTS: Sera and SF from RA patients reacted significantly more strongly to a 12 amino acid peptide, EFHELGDIAIAA, that shares a significant homology with collagen type IX, than did SF and sera from control groups (p < 0.0209 and p < 0.0115, respectively). In addition, the humoral responses to a 15 amino acid peptide, GGYGDGGAHGGGYGG, derived from the glycine-rich cell wall protein (GRP) 1.8, and to a 16 amino acid synthetic peptide, LGSISESRRALQDSQR, derived from the Proteus haemolysin protein were significantly stronger in RA patients compared with healthy individuals (p < 0.0001 and p < 0.0011, respectively). CONCLUSION: Our data indicate that peptide phage libraries can be used as tools for the identification of the (auto)antigen leads that may be responsible for the initiation, perpetuation, or both, of the immune response in patients with RA.     

IgA-anti-yersinia antibodies in yersinia triggered reactive arthritis.

Patients who develop reactive arthritis after yersinia enteritis are characterised by high and persisting IgA-anti-yersinia antibodies. We have further analysed the humoral immune response to yersinia in this condition. Total concentrations of IgM, IgG, IgA, and secretory IgA in the serum and specific anti-yersinia antibodies belonging to IgA1, IgA2, or secretory IgA were compared in patients with or without reactive arthritis. In the former group the serum concentration of secretory IgA and of yersinia specific antibodies in all categories studied was raised compared with the level in patients without joint symptoms; the difference was most significant for the IgA-anti-yersinia antibodies with secretory piece or with J chain. The findings suggest that the strong antibody response in the patients developing reactive arthritis is due to a chronic stimulation of the intestinal lymphoid tissue.     

Virus antibodies in serum and synovial fluid of patients with rheumatoid arthritis and other connective tissue diseases.

Rubella and influenza A (H3N2) haemagglutination inhibition (HI) antibody titres and measles complement-fixing (CF), haemagglutination inhibition (HI), haemolysis inhibition (HLI), and ribonucleoprotein gel precipitation (RNP-GP) antibody titres were studied in the serum and synovial fluid of twenty patients with rheumatoid arthritis (RA), two patients with ankylosing spondylitis, and two patients with Reiter's syndrome. Antibody titres were also studied in the serum and CSF of four patients with systemic lupus erythematosus (SLE), one patient with dermatomyositis, and in the synovial fluid only of five patients with osteoarthritic knee effusions. Antibodies were found with each serological technique used in the synovial fluid of RA patients and the antibody titres were usually at about the same level as in the serum. The mean measles (HI, HLI, and RNP-GP) antibody titres were 4 to 6 times higher in the synovial fluid of RA patients than in synovial fluid of patients with osteoarthritic knee effusions, but a corresponding difference was not found in rubella and influenza A antibody titres. The mean measles antibody titres (CF, HI, HKI, and RNP-GP) were consistently higher in the synovial fluid of RA patients without rheumatoid factor than in the synovial fluid of RA patients with rheumatoid factor. In serum this difference was observed only with measles CF titres. The mean measles, antibody titres were consistently lower in the serum and synovial fluid of the RA patients without the synovial fluid haemolytic complement than in the RA patients with this haemolytic complement. No similar differences were found in the rubella and influenza antibody titres. No significant measles antibody titres were found in the CSF of patients with SLE or dermatomyositis.     

The aminoterminal-type-III procollagen peptide and proteoglycans in serum and synovial fluid of patients with rheumatoid arthritis or reactive arthritis

Summary 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. Intra-articular glucocorticoid injection reduced the levels of propeptide and proteoglycan in synovial fluid.     

Bacterial antigens in synovial biopsy specimens in yersinia triggered reactive arthritis.

Non-viable structures of Yersinia enterocolitica O:3 were shown at the site of inflammation within mononuclear cells in the synovial membrane of eight out of 10 patients with yersinia triggered reactive arthritis. An avidin-biotin-peroxidase complex method, with a rabbit antiserum specific for Y enterocolitica O:3, was used to visualise yersinia structures. All 13 control samples were negative except for one with non-specific mast cell staining. The findings emphasise the significance of foreign material in the initiation of synovitis in reactive arthritis.     

Asialylated IgG in the serum and synovial fluid of patients with rheumatoid arthritis.

A novel enzyme linked immunosorbent assay has been developed that detects an asialylation change in the IgG molecules from patients with rheumatoid arthritis (RA) by the binding of biotinylated RCA 1 (ricin) to capture IgG. Elevated levels of asialylated IgG were detected in paired serum and synovial fluids (SF) of patients with RA. When compared with healthy controls, particularly in the SF (p less than 0.05) correlations of the asialylation change were found in paired samples (p less than 0.01) and between asialylated IgG and rheumatoid factors (p less than 0.01), C-reactive protein (p less than 0.02) and the Lee and Ritchie indices p less than 0.02 and 0.05, respectively. We found the proportion of asialylated IgG was higher in DR4 positive patients, indicating a possible association of these individuals to a sialyl transferase abnormality.     

Intestinal permeability in patients with yersinia triggered reactive arthritis.

The passive intestinal permeability of patients with yersinia triggered reactive arthritis was studied using different sized polyethylene glycols (PEGs) contained in a mixture of PEG 400 and PEG 1000. The investigation was carried out at least one year after the onset of yersinia infection, and patients had neither acute gastrointestinal nor joint symptoms. The control groups included patients with uncomplicated yersiniosis as well as healthy subjects who were either HLA-B27 positive or negative. An altered intestinal barrier function to PEG molecules was detected in patients with a history of yersinia infection compared with healthy controls. No significant differences in the permeability were found between patients with or without reactive arthritis, nor was there any association of increased permeability with HLA-B27. The passive permeability of the intestinal mucosa to the larger molecules was increased for an unexpectedly long time after the acute yersinia infection, probably contributing to the perpetuation of joint symptoms in subjects susceptible to a chronic joint disease.     

Interleukin 13 in synovial fluid and serum of patients with psoriatic arthritis

OBJECTIVES: To compare the pattern of interleukin (IL) 13 production in synovial fluid (SF) and serum of patients with psoriatic arthritis (PsA) with that in patients with rheumatoid arthritis (RA) and osteoarthritis (OA), investigating its relation to the proinflammatory cytokine IL12. METHODS: SF and serum IL13 levels were determined in 35 patients with PsA, 36 with RA, and 15 with OA. The main clinical and laboratory variables, including number of painful and/or swollen joints, Ritchie index, morning stiffness, erythrocyte sedimentation rate, level of C reactive protein, level of rheumatoid factor, and SF analysis, were also evaluated. RESULTS: SF IL13 levels were significantly higher in patients with PsA (p<0.02) or RA (p<0.012) than in patients with OA, with no significant difference between the former two. SF IL12 levels were significantly higher in patients with PsA (p<0.023) than in those with OA. Serum IL13 (p<0.0001) and IL12 (p<0.02) levels were lower in patients with PsA than in those affected by RA. Only patients with PsA had higher IL13 levels in SF than in serum (p<0.002). The IL13 SF/serum ratio was higher in the PsA group than in the group with RA (p<0.005) or OA (p<0.026). SF IL13 levels correlated with serum IL13 levels (p<0.0001) in RA and with SF IL12 levels (p<0.03) in PsA. CONCLUSIONS: In PsA, there appears to be localised production of IL13, in balance with IL12, in the inflamed joints. The distinct IL13 secretion profiles in PsA, RA, and OA may be related to the clinical pictures, reflecting the different pathogenic mechanisms involved in inflammatory and degenerative joint diseases.     

Serum and synovial fluid adenosine deaminase activity in patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis.

Adenosine deaminase activity was determined in paired samples of serum and synovial fluid taken from patients with rheumatoid arthritis (n = 12), reactive arthritis (n = 13), and osteoarthritis (n = 7), and the value of this investigation in the diagnosis of synovial swellings was assessed. Increased activity was found in the synovial fluid taken from patients with rheumatoid disease and reactive arthritis, though values were less raised in the latter. Synovial fluid taken from patients with osteoarthritis did not show significantly raised adenosine deaminase activity as compared with that of normal controls (n = 3).     

Levels of serum and synovial fluid pyridinium crosslinks in patients with rheumatoid arthritis

OBJECTIVE: To elucidate the major source of pyridinium crosslinks in rheumatoid arthritis (RA). METHODS: Serum samples were collected from 75 patients with RA and 41 healthy controls, and synovial fluid (SF) samples were collected from 20 patients with RA and 13 with osteoarthritis (OA). Paired samples of serum and SF were collected at the same time from 26 patients with RA. Levels of pyridinium crosslinks were determined by a recently developed high sensitivity assay method using high pressure liquid chromatography. RESULTS: The levels of serum pyridinoline (PYD) and serum deoxypyridinoline (DPD) were significantly higher in patients with RA than in healthy controls, and significantly correlated with laboratory variables indicating disease activity and severity. The levels of SF DPD, but not SF PYD, were significantly higher in patients with RA than in patients with OA. The levels of SF PYD and SF DPD both showed a significantly positive correlation with those of either SF interleukin 1beta or SF interleukin 6 in patients with RA. Finally, the levels of PYD, but not DPD, were higher in SF than in serum in all paired RA samples collected at the same time, with significant correlation between the members of each pair. CONCLUSION: These observations suggest than an increase of PYD in RA serum may originate mostly from affected joints and that an increase of DPD in RA serum may be influenced more by systemic bone resorption.     

类风湿关节炎患者血清滑液和滑膜组织白细胞介素-18的水平及意义

目的 研究类风湿关节炎（RA）患者血清、滑液中白细胞介素－18（IL－18）蛋白及滑膜组织IL－18mRNA表达水平，探讨其在RA致病中的作用。方法 应用双抗夹心酶免疫吸附（ELISA）法和细胞生物法分别测定RA患者血清、滑液中IL－28蛋白水平和生物活性，同时还检测NO、前列腺素E2的含量；有用半定量RT－PCR法检测膜组织IL－18m RNAG表达水平。以骨关节炎（OA）病人及因外伤截肢的正常人作对照。结果 RA患者血清、滑液中IL－18蛋白水平和生物活性均显著高于对照组，滑液中量及活化性比血清高；RA滑膜组织IL－18mRNA表达水平也明显高于对照组。结论 过度表达的IL－18参与了RA的致病过程,；选择性地抑制IL－18生物活性，将是RA治疗的新途径。     

Ciprofloxacin v placebo for treatment of Yersinia enterocolitica triggered reactive arthritis

Patients with yersinia triggered reactive arthritis were double blind randomly allocated to receive treatment with ciprofloxacin 500 mg twice daily orally or placebo during three months. The diagnosis was made by serology (specific IgA and IgG antibodies to yersinia outer membrane proteins (yops)), positive culture, and/or demonstration of Yersinia enterocolitica antigen in colon biopsy specimens. Patients were evaluated monthly during and after treatment up to 12 months. Of 18 patients enrolled, all could be evaluated for safety, 16 for efficacy. There was a tendency towards faster remission and relief of pain in those receiving ciprofloxacin. Y enterocolitica was eliminated from the gut associated lymphoid tissue in six of seven patients receiving ciprofloxacin compared with none of nine patients receiving placebo. Patients receiving placebo had more and prolonged circulating IgA antibodies against yops than patients treated with ciprofloxacin.     

Plasma and synovial fluid cAMP in patients with rheumatoid arthritis.

cAMP was measured in plasma and synovial fluid from 11 patients suffering from rheumatoid arthritis with a specific protein-binding assay. Plasma and synovial fluid values were 17.0 +/- 6.8 pmol/ml and 8.3 +/- 3.7 pmol/ml, range 5-28 pmol/ml and 5-16 pmol/ml, respectively. No correlation could be established between plasma and synovial fluid levels, plasma and disease activity, or synovial fluid and disease activity, as judged by Lansbury's index. It is concluded that it seems unlikely that synovial fluid cAMP is derived solely from plasma and that no simple relation exists between cAMP in plasma and synovial fluid and total disease activity.     

Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum

BACKGROUND: Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects. OBJECTIVES: To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity. METHODS: Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28). RESULTS: Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p<0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not with selected (adipo) cytokines. CONCLUSION: The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.     

Diagnostic value of synovial fluid analysis in children with reactive arthritis

We report on three children with pauciarticular arthritis in whom the clinical picture and serology were compatible with both arthritis reactive to infection with Yersinia or Salmonella and with Lyme arthritis. Results of analysis of synovial fluid by polymerase chain reaction for enterobacterial or borrelial sequences were negative. Immunofluorescence with specific antibodies revealed the presence of amorphous enterobacterial antigens in synovial fluid cells. Since this staining did not reveal enterobacterial morphology, we infected synovial fluid cells of two children with juvenile rheumatoid arthritis in vitro with Yersinia or Salmonella. After 24 h typical rods were observed, but after about 1 week amorphous antigen similar to what had been found in the three patients was seen. In cases of reactive arthritis with ambiguous results of serological testing the diagnosis may be confirmed by demonstration of enterobacterial antigens in synovial fluid.