Light诱导类风湿关节炎滑膜细胞向破骨细胞转化

目的 观察Light在类风湿关节炎(RA)滑膜细胞向破骨细胞转化过程中的作用.方法 取8例RA患者滑膜组织,胶原酶消化获取滑膜细胞,每例滑膜细胞分成5份培养,第1组加入巨噬细胞集落刺激因子(MCSF)作阴性对照,第2组加入MCSF和LIGHT,第3组加入MCSF和核因子(NF)-κB受体激动剂配体(RANKL),第4组加入MCSF、LIGHT和RANKL,第5组加入LIGHT.体外培养2周后,行抗酒石酸酸性磷酸酶(TRAP)染色,F肌动蛋白(F-actin)染色以及象牙片上骨吸收陷窝观察破骨细胞的形成和活性.结果 第1组和第5组TRAP(-),F-actin(-),象牙片上无骨吸收陷窝形成;第2组TRAP(+),F-actin(+),骨陷窝形成(+),多核破骨细胞呈圆形和椭圆形,体积较小,骨陷窝分散,体积较小;第3组TRAP(++).F-actin(++),骨陷窝形成(++),多核破骨细胞体积大,骨陷窝较多,体积大,形态不规则;第4组TRAP(+++),F-actin(+++),骨陷窝形成(++++),多核破骨细胞更多,骨陷窝大且有融合趋势.结论 Light能诱导RA滑膜细胞向破骨细胞转化,并能促进RANKL诱导滑膜细胞向破骨细胞转化的能力.     

Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis

OBJECTIVE: To examine synovial fluid as a site for generating citrullinated antigens, including the candidate autoantigen citrullinated alpha-enolase, in rheumatoid arthritis (RA). METHODS: Synovial fluid was obtained from 20 patients with RA, 20 patients with spondylarthritides (SpA), and 20 patients with osteoarthritis (OA). Samples were resolved using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by staining with Coomassie blue and immunoblotting for citrullinated proteins, alpha-enolase, and the deiminating enzymes peptidylarginine deiminase type 2 (PAD-2) and PAD-4. Proteins from an RA synovial fluid sample were separated by 2-dimensional electrophoresis, and each protein was identified by immunoblotting and mass spectrometry. Antibodies to citrullinated alpha-enolase peptide 1 (CEP-1) and cyclic citrullinated peptide 2 were measured by enzyme-linked immunosorbent assay. RESULTS: Citrullinated polypeptides were detected in the synovial fluid from patients with RA and patients with SpA, but not in OA samples. Alpha-enolase was detected in all of the samples, with mean levels of 6.4 ng/microl in RA samples, 4.3 ng/microl in SpA samples, and <0.9 ng/microl in OA samples. Two-dimensional electrophoresis provided evidence that the alpha-enolase was citrullinated in RA synovial fluid. The citrullinating enzyme PAD-4 was detected in samples from all 3 disease groups. PAD-2 was detected in 18 of the RA samples, in 16 of the SpA samples, and in none of the OA samples. Antibodies to CEP-1 were found in 12 of the RA samples (60%), in none of the SpA samples, and in 1 OA sample. CONCLUSION: These results highlight the importance of synovial fluid for the expression of citrullinated autoantigens in inflammatory arthritis. Whereas the expression of citrullinated proteins is a product of inflammation, the antibody response remains specific for RA.     

Synovial permeability in rheumatoid arthritis

In patients with rheumatoid arthritis, as well as in persons with other kinds of synovitis, proteins enter the knee joint more rapidly than in normal individuals (P < 0.001). The rheumatoid synovium, however, is less permeable to small molecules (tritiated water, P < 0.02; urate, P < 0.05; and glucose, P < 0.002) than is the normal joint lining. This difference is explained if rheumatoid microvascular changes enhance synovial permeability to proteins while coexisting interstitial changes diminish synovial permeability to smaller molecules.     

Synovial lymphocyte responses to microbial antigens differentiate the arthritis of enteric reactive arthritis from the arthritis of inflammatory bowel disease

Synovial lymphocyte responses to microbial antigens were measured by the 3H-thymidine uptake method in 5 patients with bacteriologically defined enteric reactive arthritis and 7 patients with arthritis associated with inflammatory bowel disease. All the patients with enteric reactive arthritis had maximal synovial lymphocyte responses to the relevant enteric antigen; in contrast, the synovial lymphocytes of the patients with inflammatory bowel disease all responded maximally to nonenteric antigens.     

Synovial tissue interleukin-18 expression and the response to treatment in patients with inflammatory arthritis

OBJECTIVE: To measure synovial tissue interleukin-18 (IL-18) expression in patients with inflammatory arthritis, and to identify associations with serum levels, disease activity, and response to treatment. METHODS: Synovial tissue biopsies and serum samples were obtained from patients with early, active, rheumatoid arthritis (RA) (n = 12), undifferentiated seronegative arthritis (SnA) (n = 9), psoriatic arthritis (PsA) (n = 5), and reactive arthritis (ReA) (n = 2) before and one year after introduction of disease modifying antirheumatic drug (DMARD) treatment. Osteoarthritis (OA) tissues were compared. Tissue IL-18 expression was determined after immunohistochemical staining using a semiquantitative scale. Serum IL-18 was measured by enzyme linked immunosorbent assay. RESULTS: Before treatment was started, tissue IL-18 expression was increased in each diagnostic group compared with OA (p<0.05). Tissue IL-18 expression was correlated with serum C reactive protein levels (r = 0.53, p = 0.003) but not with serum IL-18. After DMARD treatment, 12 patients (five RA, four SnA, three PsA) were re-evaluated. Decreases in tissue IL-18 expression were observed in eight, although the trend did not reach significance (p = 0.068). Changes in tissue IL-18 expression were correlated with changes in serum IL-18 (r = 0.62, p = 0.041) and C reactive protein (r = 0.72, p = 0.009). CONCLUSIONS: Synovial tissue IL-18 expression was correlated with disease activity in inflammatory arthritis. After treatment, tissue levels changed in parallel with changes in serum IL-18 and with changes in the acute phase response. These observations support a role for IL-18 in the pathophysiology of inflammatory arthritis.     

Synovial cyst in juvenile idiopathic arthritis

Small synovial cysts are a common manifestation of juvenile idiopathic arthritis; large brachial cysts, however, are a rare sign of the disease and they must be differentiated from other soft tissue swelling which are not related to articular involvement. We describe the case of three children with juvenile idiopathic arthritis who came to our attention with large synovial cysts. Ultrasonographic examination and MRI were performed in all cases, showing the real nature of the swelling and the connection to the joint. In all cases, swelling reduced and then disappeared with control of disease activity; in two cases, they reappeared in coincidence with a severe relapse of juvenile idiopathic arthritis.Brachial swellings represent a diagnostic challenge because they can be the clinical expression of a variety of diseases. In children with juvenile idiopathic arthritis who present with a sudden swelling of the upper arm, synovial cysts must be considered in the diagnostic workout, because they are a possible rare manifestation of juvenile idiopathic arthritis.     

Synovial permeability in rheumatoid arthritis.

In patients with rheumatoid arthritis, as well as in persons with other kinds of synovitis, proteins enter the knee joint more rapidly than in normal individuals (P less than 0.001). The rheumatoid synovium, however, is less permeable to small molecules (tritiated water, P less than 0.02; urate, P less than 0.05; and glucose, P less than 0.002) than is the normal joint lining. This difference is explained if rheumatoid microvascular changes enhance synovial permeability to proteins while coexisting interstitial changes diminish synovial permeability to smaller molecules.     

Synovial fluid lymphocytes in rheumatoid arthritis

There is significant evidence implicating immunologic mechanisms in the pathogenesis of rheumatoid arthritis (RA). To investigate the possibility that a cellular imbalance of T and B lymphocytes plays a role in perpetuating synovitis, an examination of the peripheral blood and synovial fluid lymphocytes of patients with seropositive rheumatoid arthritis was undertaken. A significant lymphopenia was encountered in RA patients, with values approximately midway between those in normal controls and the severe lymphopenia seen in a group of patients with systemic lupus erythematosus. A significantly greater diminution of T than B cells was noted in RA, and normal percentage distributions of lymphocytes in peripheral blood were documented. Normal percentages of T and B cells, similar to those in peripheral blood, were found in synovial fluids of patients with seropositive RA, seronegative RA, osteoarthritis, and gout. Two seropositive patients exhibited synovial fluid, but not peripheral blood, lymphocytes that stained both for IgG and IgM. These cells regenerated predominantly IgM after trypsinization and short-term culture with significant diminution of cells staining for IgG. It is postulated that double staining was secondary to surface immunoglobulins with rheumatoid factor activity binding intraarticular IgG. Such cells were not detected in peripheral blood in any of the groups of patients studied.     

Synovial cyst in juvenile idiopathic arthritis

Small synovial cysts are a common manifestation of juvenile idiopathic arthritis; large brachial cysts, however, are a rare sign of the disease and they must be differentiated from other soft tissue swelling which are not related to articular involvement. We describe the case of three children with juvenile idiopathic arthritis who came to our attention with large synovial cysts. Ultrasonographic examination and MRI were performed in all cases, showing the real nature of the swelling and the connection to the joint. In all cases, swelling reduced and then disappeared with control of disease activity; in two cases, they reappeared in coincidence with a severe relapse of juvenile idiopathic arthritis. Brachial swellings represent a diagnostic challenge because they can be the clinical expression of a variety of diseases. In children with juvenile idiopathic arthritis who present with a sudden swelling of the upper arm, synovial cysts must be considered in the diagnostic workout, because they are a possible rare manifestation of juvenile idiopathic arthritis.     

Synovial tissue analysis in rheumatoid arthritis

In rheumatoid arthritis, synovial tissue is easily accessible for systematic analysis. Blind needle biopsy is a simple and safe procedure, but is restricted to smaller tissue samples. Arthroscopic biopsy is also safe but is more complicated as it allows access to most sites in the joint and provides adequate tissue for extensive laboratory investigations. Synovial tissue analysis has been successfully applied to studies of disease mechanisms, response to treatment and prognosis. The immuno-histological features in synovial tissue have consistently reflected disease status. Synovial tissue analysis has been particularly informative in the study of novel therapeutic agents.     

Synovial cysts in juvenile rheumatoid arthritis.

In a case of juvenile rheumatoid arthritis with large synovial cysts, cyst fluid aspiration was performed to relieve pain, but recurrence was prevented with salicylate therapy alone. The mechanism of formation of synovial cysts is discussed.     

Synovial membrane diagnostic assessment in rheumatoid arthritis

Rheumatoid arthritis (RA) is the most frequent inflammatory rheumatic disease. At the beginning of the disease, where, based on today's knowledge the therapeutic possibilities are largest, the diagnostic methods do not permit a differentiated estimation of the prognosis. Conventional x-rays are mostly normal and serum markers unspecific. So far--in contrast to other diseases--only little information had been drawn from the pathomorphologic substrate "synovialis" itself to assess the prognosis. Reasons therefor were found in difficulties in obtaining synovial tissue besides surgical interventions, particularly in patients with early arthritis. By minimalizing the diagnostic instruments and improvement of the technique, synovial tissue sampling in RA has become minimally invasive and it is even possible to perform on the smallest joints, such as finger joints. Hereby, synovial analysis is open for detecting pathways of inflammation and joint destruction, which might support the advancement of new therapeutic strategies, followed by a better prognosis and outcome of RA.     

Synovial fluid in seronegative juvenile rheumatoid arthritis

Synovial fluid of 20 children with seronegative juvenile rheumatoid arthritis (JRA) and 20 patients with other joint pathology was examined for levels of total hemolytic complement and selected components, immune complexes, and α₂-macroglobulin (α₂-M). When adjusted for total protein, synovial levels of total hemolytic complement, C3, C4, and α₂-M did not differ significantly in the two groups. The concentrations of IgM and IgG were elevated in the JRA synovial fluid, but immune complexes were not increased when compared with the non-JRA group as determined by the Raji cell technique. α₂-M activity against substrates of C1 esterase was absent. Therefore, evidence of specific increase in immune complexes and complement activation was sought but not found, suggesting that they may not be a major factor in the pathogonesis of seronegative, pauciarticular JRA.     

Synovial pathologic changes in spontaneous canine rheumatoid-like arthritis

The synovial fluid and membrane were studied in 10 dogs meeting the American Rheumatism Association criteria for classic human rheumatoid arthritis (RA). Light microscopic pathologic features were consistent with those found in the human disease. Neutrophilic infiltration of synovium was somewhat more prominent than in chronic human RA, and activated lymphocytes in fluid or membrane were less frequent. The proliferative and plasma cell reaction seemed identical. Electron microscopy (EM) suggested microvascular injury with findings which included electron dense deposits in the vessel walls of 2 dogs. Seven dogs had meshworks of 20-25 mm tubules in tubuloreticular structures (TRS) similar to those seen in human systemic lupus erythematosus and only occasionally in human RA. There were also crystalline arrays of tubules, a configuration previously reported in tumors and virus infections and possibly suggestive of a cellular reaction to virus infection. To date no initiating agent has been identified, but this spontaneous canine disease which is very similar to human RA can provide a valuable model in which to examine pathogenesis of chronic arthritis.     

Synovial fibroblasts: key players in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that primarily affects the joints and ultimately leads to their destruction. The involvement of immune cells is a general hallmark of autoimmune-related disorders. In this regard, macrophages, T cells and their respective cytokines play a pivotal role in RA. However, the notion that RA is a primarily T-cell-dependent disease has been strongly challenged during recent years. Rather, it has been understood that resident, fibroblast-like cells contribute significantly to the perpetuation of disease, and that they may even play a role in its initiation. These rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints. A number of studies have demonstrated that RASFs show alterations in morphology and behaviour, including molecular changes in signalling cascades, apoptosis responses and in the expression of adhesion molecules as well as matrix-degrading enzymes. These changes appear to reflect a stable activation of RASFs, which occurs independently of continuous exogenous stimulation. As a consequence, RASFs are no longer considered passive bystanders but active players in the complex intercellular network of RA.