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ID PMID Title PublicationDate abstract
12355445 Expression of FcgammaRIII is required for development of collagen-induced arthritis. 2002 Oct Circulating immune complexes are implicated in the pathogenesis of rheumatic immune disorders and the interaction of these immune complexes with IgG Fc receptors (FcgammaR) seems to be a determining step in the initiation of the inflammatory process. Mice deficient in the FcRgamma-chain, and thus lacking multiple FcR, have previously been shown to be protected from collagen-induced arthritis (CIA). However, the relative contribution of the different FcgammaR has not been identified. In this study, we investigated the expression and contribution of FcgammaRIII, the activating low-affinity FcgammaR in the development of CIA. Wild-type and FcgammaRIII-deficient DBA/1 (FcgammaRIII(-/-)) mice were immunized with bovine collagen type II (BCII) in Freund's complete adjuvant and arthritis development was evaluated by clinical and histological examinations. We found that FcgammaRIII(-/-) mice developed virtually no arthritis in contrast to wild-type mice, the majority of which developed severe CIA. Although resistant to CIA, the humoral and cellular responses to BCII in FcgammaRIII(-/-) mice were similar to that seen in wild-type controls. FcgammaRIII expression was studied on sections from normal joints of FcgammaRII-deficient DBA/1 mice stained with the mAb 2.4G2, specific for FcgammaRII and FcgammaRIII. FcgammaRIII was demonstrated in cells of the lining and sublining layer of the synovial membrane. We conclude that development of CIA requires FcgammaRIII and that expression of FcgammaRIII on synovial cells may contribute to the antibody-triggered inflammation in joints.
14740451 B cell activation in rheumatoid arthritis patients under infliximab treatment. 2003 Nov OBJECTIVE: To determine whether anti-TNF alpha (infliximab) treatment affects B cell activation in patients with rheumatoid arthritis (RA) METHODS: B cell activation was analyzed in fifteen anti-TNF-treated RA patients. CD23 expression was used as a B cell activation marker and was studied before and after three months of infliximab treatment. PBMC were stimulated with anti-CD3 mAb during 18 h and were separated by rosseting into E+ and E-cells. B cells were assessed in E-population by double staining with CD19 and CD23. ELISA assays were used to assess both soluble TNF alpha and circulant immune complexes (CIC) containing TNF alpha. We also used B cells from tonsils to establish the relationship between B cell activation and TNF alpha CIC. RESULTS: The proportion of B cells expressing CD23 was higher before infliximab exposure than after treatment (48.3 +/- 16.7 versus 29.5 +/- 12.5, p = 0.007). T-B cell interactions were assessed by means of blocking antibodies to CD154, CD40, CD69, and CD18; these interactions were not specially affected by infliximab treatment. We could demonstrate CIC containing TNF alpha after infliximab treatment, these CIC, similarly to others IgG-containing immune complexes, were capable to downregulate CD23 on B cells. CONCLUSIONS: Infliximab treatment in RA downregulates CD23 expression on T-cell activated B cells. This downregulation is connected with the presence of CIC containing TNF alpha. Presumably, the Fc gamma RIIb1 endows IgG-containing immune complexes, as TNF alpha-anti-TNF alpha, with the capacity to regulate B cells and inflammatory cells.
11987981 Immune function in patients with rheumatoid arthritis treated with etanercept. 2002 Apr Etanercept, a recombinant human tumor necrosis factor (TNF) inhibitor that binds both soluble and cell-bound TNF, has been shown to reduce disease activity and inhibit joint destruction when administered to patients with rheumatoid arthritis (RA). Because TNF receptors are found on many types of cells that modulate the immune response, we evaluated the general immune function of a subset of RA patients in a blinded clinical study. No significant differences were seen between patients treated with etanercept or placebo in the surface antigen phenotypes of peripheral blood leukocytes, T cell proliferative responses, neutrophil function, delayed-type hypersensitivity (DTH) reactions, serum immunoglobulin levels, or incidence of infections. Although this observational study was relatively small and could detect only major changes in immunological status, the stability of immune function over time in patients receiving etanercept corroborates the findings in clinical studies, which suggest that etanercept does not alter overall global immune function.
12846054 Clinical outcome and survival of secondary (AA) amyloidosis. 2003 May OBJECTIVE: In order to predict the clinical outcome of secondary (AA) amyloidosis patients with rheumatic diseases, we studied the clinical features at presentation of AA amyloidosis. METHODS: We investigated the clinical characteristics and survival of 42 patients with biopsy-proven AA amyloidosis who were followed up in our department from 1983 to 2001. RESULTS: A presenting factor which adversely influenced clinical outcome was a raised serum creatinine concentration at the time AA amyloidosis was diagnosed. Eight of 42 patients survived for 10 years or more after the presentation of AA amyloidosis, while 24 patients had died within 10 years. At the diagnosis of AA amyloidosis, cardiac involvement was detected in 11 of 24 non-survivors, whereas it was not detected in any of the 8 long-term survivors. Estimated survival at 5 years was 31.3% in those who had cardiac involvement, and was 63.3% in those who had no cardiac involvement at the presentation of AA amyloidosis. CONCLUSION: Our results indicate that clinical outcome is related to renal function and cardiac involvement at the time AA amyloidosis is diagnosed. Amyloid-related cardiac involvement is one of the unfavorable predictive factors in AA amyloidosis patients.
12069368 Effect of cod liver oil on symptoms of rheumatoid arthritis. 2002 Mar In this pilot study, 43 patients with rheumatoid arthritis ingested 1 g of cod liver oil (one capsule) daily for 3 months. Decreases occurred in morning stiffness (52.4%; P<10(-3)), painful (42.7%) and swollen (40%) joints (P= 10(-3) each), and pain intensity (67.5%). Ratings of "good" or "very good" were awarded by 68% of the patients for efficacy and by 95% for tolerability. Eleven patients reported nonsevere adverse effects that in 3 cases may have been related to the study preparation. Cod liver oil can be recommended for the treatment of rheumatoid arthritis.
11953964 Delay to institution of therapy and induction of remission using single-drug or combinatio 2002 Apr OBJECTIVE: To study the impacts of 1) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two treatment strategies (treatment with a combination of DMARDs or with a single drug), and 3) the presence of HLA-DRB1 alleles (shared epitope) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis (RA). METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomly assigned to receive either 1) a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or without prednisolone. The presence of a shared epitope was tested for in 165 of the 178 patients completing the study. The additional variables of age, sex, presence of rheumatoid factor, number of fulfilled American College of Rheumatology criteria for the classification of RA, and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years. RESULTS: The delay to therapy (cut point of 4 months) was the only significant predictor for remission in patients treated using the single-DMARD strategy, while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy. The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short (0-4 months) and long (>4 months) delay periods (11 of 26 patients and 22 of 53 patients, respectively [approximately 42% in each group]), while the corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%) and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not related to the induction of remission. CONCLUSION: The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in early RA.
15172038 Safety overview of new disease-modifying antirheumatic drugs. 2004 May Beginning in 1998, a surge of new agents has expanded treatment options for rheumatoid arthritis (RA) patients. Although the disease modifying potential of these agents is encouraging, their use must be weighed against an evolving array of new safety concerns. Because of the popularity of these agents with patients and rheumatologists alike, clinicians must be prepared to discuss the potential risks associated with novel disease-modifying antirheumatic drugs and biologic therapies as they begin to appear with greater frequency in practice. This article discusses the safety issues arising from clinical trial and postmarketing experience with several new and commonly used agents, with specific emphasis on adalimumab, etanercept, infliximab, anakinra, and leflunomide.
12448094 [Anesthesia using laryngeal mask in orthopedic surgery]. 2002 Oct Experience of application of laryngeal mask (LM) for realization of artificial pulmonary ventilation in patients in complicated conditions for trachea intubation in orthopedic surgery allows to recommend it as an alternative method. Simplicity of establishment, absence of complications after application of LM were noted.
12189455 ACTH, cortisol and prolactin in active rheumatoid arthritis. 2002 Aug Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1 beta and TNF-alpha circadian rhythms have been studied in active RA (aRA) to evaluate a possible relationship between the neuroendocrine system and immunological activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1 beta and TNF-alpha levels were determined in aRA patients and in control subjects at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1 beta and TNF-alpha reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This study provides evidence that in aRA there could be a temporary and probably causal relationship between diurnal disease activity, hormonal disequilibrium and cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and cytokines) as opposed to levels of anti-inflammatory hormones could be responsible for the diurnal rhythm of activity disease observed in aRA patients.
15172049 Clinical experience with inhibition of interleukin-6. 2004 May Rheumatoid arthritis (RA) is a systemic disease that is associated with increased mortality and morbidity. Prognosis depends on disease severity and response to treatment. Those patients whose diseases are refractory to treatment with disease-modifying antirheumatic drugs (DMARDs) and have persistent inflammation have reduced survival similar to patients with triple-vessel coronary artery disease and Hodgkin's lymphoma. Although DMARDs reduce inflammation and improve symptoms, they do not improve long-term prognosis. Chronic synovial inflammation results in damage to the articular cartilage and adjacent bone. Consequently,after 10 years of disease most patients develop significant disability due to joint damage. Interleukin-6 (IL-6) is a key mediator of inflammation in RA. Inhibition of IL-6 reduces synovitis and improves symptoms. Therapies targeting IL-6 are promising new treatments for RA.
15124248 Economic evaluation of folate supplementation during methotrexate treatment in rheumatoid 2004 May OBJECTIVE: To determine cost-effectiveness of folic or folinic acid supplementation in patients with rheumatoid arthritis (RA) who started methotrexate (MTX) treatment. METHODS: An economic evaluation, performed alongside a randomized, double blind, placebo controlled trial with followup of 48 weeks. Patients started MTX with placebo (n = 137), folic acid (n = 133), or folinic acid (n = 141). Outcome measures were drug survival and quality-adjusted life-years (QALY), measured with the EuroQol questionnaire. Both medical and nonmedical costs were analyzed. RESULTS: Drug survival after 48 weeks was 60% for placebo, 81% for folic acid, and 87% for folinic acid. QALY during a 48 week period were 0.55 (95% CI 0.52-0.58) in the placebo group, 0.55 (95% CI 0.52-0.58) in the folic acid group, and 0.58 (95% CI 0.56-0.60) in the folinic acid group. Mean medical costs were 1398 US dollars (placebo), 1409 US dollars (folic acid), and 1776 US dollars (folinic acid). Mean total costs were 3339 US dollars, 3632 US dollars, and 3296 US dollars, respectively. CONCLUSION: In terms of resource deployment, no statistically significant difference was found between the 3 strategies. The preferred strategy consists of folic acid supplementation because of improved drug survival.
15000271 Changes in Helicobacter pylori status in patients with rheumatoid arthritis under non-ster 2004 Feb BACKGROUND: The role of Helicobacter pylori infection in rheumatoid arthritis (RA) patients during treatment with non-steroidal anti-inflammatory drugs (NSAID) is still unclear. METHODS: By means of endoscopy and biopsy, gastroduodenal lesions and H. pylori status were repeatedly examined in 88 RA patients at intervals ranging from 26 to 49 months. Histology and culture were applied to determine H. pylori status. Serial changes in gastroduodenal lesions and histologic score for mucosal atrophy were compared among groups classified by initial and second H. pylori status. RESULTS: There were 28 patients with continuously positive H. pylori infection (CP group), 33 patients with continuously negative H. pylori infection (CN group), 7 patients in whom H. pylori status became negative (PN group), and 20 patients in whom H. pylori status could not be determined (UD group). Age, duration and species of NSAID, disease activity of RA, gastroprotective drugs applied and the prevalence of gastroduodenal mucosal lesions were not different among the groups at either the initial or the second examination. In the PN group, the score for mucosal atrophy at the second examination was significantly lower than at the initial examination, whereas no difference was found for the CP, CN and UD groups. Overall, histologic score for mucosal atrophy was higher in H. pylori-positive patients than in H. pylori-negative patients at both initial and second examination. CONCLUSIONS: In RA patients using NSAIDs, H. pylori infection may not affect the course of gastroduodenal lesions and activity of RA, but the infection contributes to mucosal atrophy.
11959761 Characterisation of the cell type-specificity of collagenase 3 mRNA expression in comparis 2002 May OBJECTIVE: To study the pattern and cell type-specificity of collagenase 3, membrane-type 1 matrix metalloproteinase (MT1-MMP), and gelatinase A mRNA expression in the synovial membrane in rheumatoid arthritis (RA). METHODS: The mRNA expression of collagenase 3, MT1-MMP, and gelatinase A was characterised by northern blot analysis, reverse transcriptase-polymerase chain reaction, and in situ hybridisation. In situ hybridisation was performed in combination with the immunohistochemical detection of cell type-specific antigens. RESULTS: Synovial membrane specimens from 19 of 21 patients with RA expressing collagenase 3 mRNA were positive for MT1-MMP and gelatinase A mRNA. In control samples from patients without destructive inflammatory joint diseases collagenase 3 mRNA was not expressed and only in two of seven cases was a coexpression of MT1-MMP and gelatinase A mRNA detected. Fibroblast-like cells of the synovial membrane were found to be the predominant source of collagenase 3, MT1-MMP, and gelatinase A mRNA expression in lining and sublining layers as well as at the synovial membrane-cartilage interface. Additionally, the expression of MT1-MMP mRNA was detected in endothelial cells. Collagenase 3 mRNA expression was found in about 5% of CD68 positive macrophages. CONCLUSIONS: Collagenase 3 mRNA is expressed simultaneously with MT1-MMP and gelatinase A mRNA in fibroblast-like cells of the synovial membrane in RA. These results suggest (a) a broad extracellular proteolytic potential of fibroblast-like cells and (b) an important role of cell surface associated procollagenase 3 activation by MT1-MMP and gelatinase A for cartilage degradation by invading fibroblast-like cells.
12730031 Temporomandibular joint function in patients with longstanding rheumatoid arthritis - I. R 2003 Mar 27 PURPOSE: Temporomandibular joint (TMJ) dysfunction in rheumatoid arthritis (RA) occurs in 2 % to 86 % of RA patients. Dental factors possibly contributing to the development of TMJ dysfunction in RA patients have rarely been investigated in controlled studies. The present clinical study aimed 1) to compare patients with active, longstanding RA and healthy control subjects matched for age, sex, periodontal risk factors, dental and prosthetic status in order to obtain data on the prevalence of TMJ dysfunction in dentate RA patients and 2) to investigate a possible relationship between RA activity, general functional state and the severity of TMJ involvement. METHODS: 50 RA patients (38 F, 12 M; 54 +/- 9 years) were compared with 101 control subjects (76 F, 25 M; 54 +/- 11 years) with regard to dental, periodontal and prosthetic status and clinical TMJ findings as measured by the Helkimo indices. Clinical evaluation of RA patients included serological parameters, pain as measured by visual analog scale (VAS), a 28-joint count, a radiological destruction score, a functional status and measurement of grip strength. RESULTS: The sum of carious, missing and filled teeth was similar in both groups. RA patients had more missing teeth (p < 0.01), more gingival bleeding, deeper pockets and more attachment loss (p < 0.0001). They showed no differences with regard to the mean number of occluding pairs of teeth, tooth support, the percentage of dentures, the grade of prosthetic support. 36 % of RA patients had a unilaterally shortened dental arch compared with 11.9 % in controls (p < 0.05). 32 % of RA patients and 27.7 % of the control subjects reported TMJ or facial pain. The mean VAS was 50 +/- 19 for RA patients and 52 +/- 21 for controls. The anamnestic data and the clinical symptoms grouped according to the Helkimo index showed no significant differences between both subject groups. However, the maximal mouth opening capacity in RA patients was significantly lower (40.6 +/- 6.5 mm) than in controls (45.8 +/- 5.5 mm; p < 0.001). Analysis of the Helkimo symptom groups revealed a significantly reduced mobility index in the RA group and impaired TM-joint function in controls (p < 0.05). Grip strength was significantly correlated with mouth opening capacity, TMJ pain with tooth support. CONCLUSION: The prevalence of TMJ dysfunction in dentate patients with longstanding RA does not exceed that of healthy controls when structural risk factors predisposing to the development of temporomandibular dysfunction are taken into consideration. Maintaining adequate tooth support might help to prevent progressive TMJ impairment in the course of disease.
12649029 Symmetrical vs asymmetrical total knee replacement--a medium term comparative analysis. 2003 Mar Modifications of established implants can result in deleterious effects, as with the Capitol and the matt coated Exeter hips. In 1991 the Kinemax plus modification of the Kinematic knee was introduced in Bristol, the design changes having been made to reduce patello-femoral complications. We carried out a comparative analysis of the prospective recorded data on a consecutive series of 182 total knee replacements (95 Kinematic and 87 Kinemax plus knees) performed between 1991 and 1993. The same instrumentation and surgical technique was used. Since the design had introduced a broader trochlear, offset patella and had changed from an asymmetrical to a symmetrical femoral component, particular attention was paid to tracking and range of movement. All patients were reviewed at 5 years using the Bristol knee score and radiographs. There was no difference in the overall score (both prosthesis scoring 85-86) but the Kinemax plus group with a symmetrical trochlear had a significantly greater improvement in the range of movement (14 degrees as opposed to 4 degrees; P<0.05). In addition, secondary intervention for mal-tracking was significantly less in the Kinemax group. No deleterious effect of the changed geometry was observed. It is concluded that the introduction of a symmetrical femoral component with an offset patella reduced patello-femoral complications without detectable disadvantages.
12180720 A randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arth 2002 Aug OBJECTIVE: To evaluate the efficacy and tolerability of the highly selective cyclooxygenase-2 (COX-2) inhibitor etoricoxib for the treatment of rheumatoid arthritis (RA). METHODS: A double blind, randomized, placebo and active comparator controlled, 12 week study conducted at 88 US sites. Eligible patients were chronic nonsteroidal antiinflammatory drug (NSAID) users with clinical worsening of RA upon withdrawal of prestudy NSAID. Patients received either placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily (2:2:1 allocation ratio). Primary efficacy measures: patient and investigator global assessments of disease activity and direct assessment of arthritis by counts of tender and swollen joints. Key secondary measures: patient global assessment of pain, the Stanford Health Assessment Questionnaire, and the percentage of patients both completing the study and meeting the ACR20 criteria. Tolerability was assessed by tabulation of adverse events and routine laboratory evaluations. RESULTS: In all, 816 patients were randomized (placebo = 323, etoricoxib = 323, naproxen = 170), and 448 completed 12 weeks of treatment (placebo = 122, etoricoxib = 230, naproxen = 96). Compared with patients receiving placebo, patients receiving etoricoxib and naproxen showed significant improvements in all efficacy endpoints (p < 0.01). Compared with patients receiving naproxen, patients receiving etoricoxib demonstrated significant improvements (p < 0.05) on all primary endpoints and most other endpoints including ACR20 criteria. The percentage of patients who achieved an ACR20 response and who completed the study was 21%, 53%, and 39% in the placebo, etoricoxib and naproxen groups, respectively. Etoricoxib and naproxen were both generally well tolerated. CONCLUSION: In this study, etoricoxib 90 mg once daily was more effective than either placebo or naproxen 500 mg twice daily for treating patients with RA over 12 weeks. Etoricoxib 90 mg was generally well tolerated in patients with RA.
12135732 Ring up the curtain on DING proteins. 2002 Jul 31 DING proteins have a characteristic DINGGG- or closely related N-terminal sequence. One is found in human synovial fluid, and may be associated with rheumatoid arthritis. Other examples have receptor or signalling roles in various human and animal cells, or are involved in biomineralisation, and several of them bind to phytochemicals. As plant DING proteins have recently been discovered, we hypothesise that the DING protein-phytochemical association may represent one aspect of a ubiquitous receptor-linked signalling system. Several microbial proteins related to DING proteins have phosphatase activity, which may relate to biomineralisation in eukaryotic systems. Plant DING proteins and their microbial relatives may elicit allergic responses leading to arthritic disease.
12942699 Early onset and effective inhibition of bone resorption in patients with rheumatoid arthri 2003 Jul OBJECTIVE: To investigate the effect of the tumour necrosis factor alpha antibody infliximab on bone metabolism in patients with rheumatoid arthritis (RA). METHODS: Twelve RA patients with active disease on a constant dose of methotrexate were treated with a single infusion of infliximab (10 mg/kg BW). Serum beta-CrossLaps and serum osteocalcin as markers of bone resorption and formation were measured two days and one day before and one and 14 days after infliximab infusion with an electrochemiluminiscence immunoassay. RA disease activity was determined using the Disease Activity Score (DAS) and the ACR-response criteria. RESULTS: Infliximab treatment significantly reduced serum beta-CrossLaps levels from 0.29 +/- 0.13 (mean +/- SD) ng/ml at study entry to 0.17 +/- 0.09 pg/ml one day after infusion (p < 0.005). At day 14 serum beta-CrossLaps levels were still significantly lower compared to pre-treatment levels (0.24 +/- 0.13 pg/ml, p < 0.05). In contrast, serum osteocalcin levels remained unchanged during the observation period (17.8 +/- 9.8 vs 18.2 +/- 9.9 vs 18.6 +/- 12.1 ng/ml, respectively). All but one patient improved clinically after infliximab infusion and the DAS dropped significantly from 6.5 +/- 0.9 prior to treatment to 5.8 +/- 1.3 and 5.0 +/- 1.3 at Day one and 14 days after treatment, respectively. Four patients showed an ACR 20-response one day after therapy and 10 patients 14 days after therapy. CONCLUSION: Infliximab might have potential to inhibit generalised bone loss in patients with RA in addition to its clinical efficacy in reducing disease activity and inhibiting joint destruction.
15240743 IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross- 2004 Jul 15 To characterize the molecules responsible for synovial fibroblast-T lymphocyte (TL) cross-talk in rheumatoid arthritis (RA), synovial fibroblasts from patients with established RA (RASFibs) were cocultured with TLs from peripheral blood of early RA patients (RAPBTL). TLs from peripheral blood of healthy controls and from synovial fluid of RA served as controls. Adhesion molecules and cytokines were determined by flow cytometry, ELISA, and real-time PCR. RAPBTL (n = 20) induced an up-regulation of ICAM-1, intracellular IL-8, IL-6, IL-15, and surface IL-15 in cocultured RASFibs. In turn, RAPBTL showed an up-regulation of TNF-alpha, IFN-gamma, IL-17, CD25, and CD69 expression. Responses seen with TLs from peripheral blood of healthy controls (n = 20) were significantly lower, whereas responses with TLs from synovial fluid of RA (n = 20) were maximal. Blocking Abs to IL-15 and CD54, but not an isotype-control Ab, down-regulated the increased TL cytokine and activation marker expression. Abs to CD69, CD11a, IL-17, TNF-alpha, and IFN-gamma significantly decreased the up-regulation of RASFib cytokine and CD54 expression. Cocultures using 0.4- micro m inserts did not result in up-regulation of surface molecules or cytokines. Methotrexate significantly inhibited RASFib/TL cross-talk signals and decreased adhesion of TL to RASFibs. In summary, RASFib production of IL-15 induces the proinflammatory cytokines TNF-alpha, IFN-gamma, and IL-17 in cocultured TLs through a cell contact-dependent mechanism. In turn, these cytokines stimulate the expression of IL-15, IL-8, and IL-6 in RASFibs, thereby creating a feedback loop that favors persistent synovial inflammation. Methotrexate seems to disrupt this loop by decreasing cell adhesion.
12373775 Mass spectrometric proteome analyses of synovial fluids and plasmas from patients sufferin 2002 Sep Differential proteome analysis is used to study body fluids from patients suffering from rheumatoid arthritis (RA), reactive arthritis (reaA) or osteoarthritis (OA). Mass spectrometric structure characterization of gel-separated proteins provided a detailed view of the protein-processing events that lead to distinct protein species present in the respective body fluids. (i) Fibrin(ogen) beta-chain degradation products, presumably plasmin-derived, appeared solely in synovial fluids (SF) from both patient collectives, (ii) calgranulin B (MRP14) was exclusively identified in SF samples derived from 5 out of 6 patients suffering from RA. Calgranulin B was not observed in synovial fluids from OA patients, nor in plasmas from either patient group. In all cases where calgranulin B was detected, calgranulin C was identified as well. (iii) Serum amyloid A protein spots were determined in plasmas and synovial fluids from patients with RA, but not in patients with OA. In addition to disease-relevant differences, interindividual differences in haptoglobin patterns of the patients under investigation were observed. Hence, in-depth proteome analysis of body fluids has proven effective for identification of multiple molecular markers and determination of associated protein structure modifications, that are thought to play a role for specifically determining a defined pathological state of diseased joints.