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ID PMID Title PublicationDate abstract
19224750 Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha ag 2009 Feb 18 CONTEXT: The risk of bacterial infection is increased in patients treated with drugs that inhibit tumor necrosis factor alpha (TNF-alpha). Little is known about the reactivation of latent viral infections during treatment with TNF-alpha inhibitors. OBJECTIVE: To investigate whether TNF-alpha inhibitors together as a class, or separately as either monoclonal anti-TNF-alpha antibodies (adalimumab, infliximab) or a fusion protein (etanercept), are related to higher rates of herpes zoster in patients with rheumatoid arthritis. DESIGN, SETTING, AND PATIENTS: Patients were enrolled in the German biologics register RABBIT, a prospective cohort, between May 2001 and December 2006 at the initiation of treatment with infliximab, etanercept, adalimumab, or anakinra, or when they changed conventional disease-modifying antirheumatic drug (DMARD). Treatment, clinical status, and adverse events were assessed by rheumatologists at fixed points during follow-up. MAIN OUTCOME MEASURES: Hazard ratio (HR) of herpes zoster episodes following anti-TNF-alpha treatment. Study aims were to detect a clinically significant difference (HR, 2.0) between TNF-alpha inhibitors as a class compared with DMARDs and to detect an HR of at least 2.5 for each of 2 types of TNF-alpha inhibitors, the monoclonal antibodies or the fusion protein, compared with conventional DMARDs. RESULTS: Among 5040 patients receiving TNF-alpha inhibitors or conventional DMARDs, 86 episodes of herpes zoster occurred in 82 patients. Thirty-nine occurrences could be attributed to treatment with anti-TNF-alpha antibodies, 23 to etanercept, and 24 to conventional DMARDs. The crude incidence rate per 1000 patient-years was 11.1 (95% confidence interval [CI], 7.9-15.1) for the monoclonal antibodies, 8.9 (95% CI, 5.6-13.3) for etanercept, and 5.6 (95% CI, 3.6-8.3) for conventional DMARDs. Adjusted for age, rheumatoid arthritis severity, and glucocorticoid use, a significantly increased risk was observed for treatment with the monoclonal antibodies (HR, 1.82 [95% CI, 1.05-3.15]), although this risk was lower than the threshold for clinical significance. No significant associations were found for etanercept use (HR, 1.36 [95% CI, 0.73-2.55]) or for anti-TNF-alpha treatment (HR, 1.63 [95% CI, 0.97-2.74]) as a class. CONCLUSION: Treatment with monoclonal anti-TNF-alpha antibodies may be associated with increased risk of herpes zoster, but this requires further study.
19451136 Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. 2010 Apr OBJECTIVES: To evaluates the diagnostic performance of the anti-CCP2, anti-CCP3 and anti-mutated citrullinated vimentin (anti-MCV) tests in differentiating rheumatoid arthritis (RA) from other forms of arthritis in a clinical setting of early arthritis. METHODS: In 917 patients with recent-onset arthritis (566 RA, 351 other diseases) and in 99 healthy controls the anti-MCV, anti-CCP2 and anti- CCP3.1 tests were performed and the test characteristics compared. RESULTS: Comparison of the tests for differentiating RA from other causes of arthritis showed a lower specificity for anti-MCV (82.9%) than for anti-CCP2 (93.4%) and anti-CCP3.1 (90.0%). Similarly, the positive likelihood ratio for anti-MCV was also lower (3.6, compared with 8.7, 5.8 for anti-CCP2 and anti-CCP3.1). The anti-MCV test had a higher sensitivity (62% vs 56.9% and 58.1%, respectively). In psoriatic arthritis, spondyloarthropathy and other arthritis anti-MCV antibodies had a prevalence of 15.2%, 13.9% and 19.4%. CONCLUSION: The diagnostic performance of the anti-MCV test in the differential diagnosis of early arthritis is lower than that of the anti-CCP tests.
19297346 Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with mod 2010 Jan BACKGROUND: The anti-interleukin (IL) 6 receptor antibody tocilizumab inhibits signalling of IL6, a key cytokine in rheumatoid arthritis (RA) pathogenesis. OBJECTIVE: To evaluate through the AMBITION study the efficacy and safety of tocilizumab monotherapy versus methotrexate in patients with active RA for whom previous treatment with methotrexate/biological agents had not failed. METHODS: This 24-week, double-blind, double-dummy, parallel-group study, randomised 673 patients to either tocilizumab 8 mg/kg every 4 weeks, or methotrexate, starting at 7.5 mg/week and titrated to 20 mg/week within 8 weeks, or placebo for 8 weeks followed by tocilizumab 8 mg/kg. The primary end point was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 24. RESULTS: The intention-to-treat analysis demonstrated that tocilizumab was better than methotrexate treatment with a higher ACR20 response (69.9 vs 52.5%; p<0.001), and 28-joint Disease Activity Score (DAS28) <2.6 rate (33.6 vs 12.1%) at week 24. Mean high-sensitivity C-reactive protein was within the normal range from week 12 with tocilizumab, whereas levels remained elevated with methotrexate. The incidence of serious adverse events with tocilizumab was 3.8% versus 2.8% with methotrexate (p = 0.50), and of serious infections, 1.4% versus 0.7%, respectively. There was a higher incidence of reversible grade 3 neutropenia (3.1% vs 0.4%) and increased total cholesterol > or =240 mg/dl (13.2% vs 0.4%), and a lower incidence of alanine aminotransferase elevations >3x-<5x upper limit of normal (1.0% vs 2.5%), respectively. CONCLUSION: Tocilizumab monotherapy is better than methotrexate monotherapy, with rapid improvement in RA signs and symptoms, and a favourable benefit-risk, in patients for whom treatment with methotrexate or biological agents has not previously failed.
20840651 Induction of interleukin-23 p19 by serum amyloid A (SAA) in rheumatoid synoviocytes. 2010 Nov In this study, we investigated the roles of serum amyloid A (SAA) in T helper 17 (Th17)-related cytokine induction in rheumatoid arthritis (RA) synoviocytes. Synoviocytes isolated from rheumatoid arthritis (RA) patients were stimulated with recombinant SAA and IL-23 expression was investigated using reverse transcriptase-polymerase chain reaction and Western blot. The involvement of mitogen-activated protein kineases (MAPKs) and nuclear factor (NF)-κB in SAA-induced interleukin (IL)-23 p19 expression was investigated using pharmacological inhibitors. In RA synoviocytes, SAA induced the expression of IL-23 p19 and p40 mRNA expression. The SAA-stimulated expression of p19 was rapid (< 3 h), and insensitive to polymyxin B treatment. This SAA-stimulated expression of IL-23 p19 was inhibited completely by inhibitors of NF-κB, p38MAPK and dexamethasone. Interestingly, the SAA-induced IL-23, p19 and p40 production was accompanied by enhanced expression of IL-1β, but not transforming growth factor-β. These results indicate that SAA is a significant inducer of IL-23 and IL-1β in RA synoviocytes and potentially activates the IL-23/IL-17 pathway in the RA synovium. Our data present a novel interaction between inflammation and autoimmunity by an acute-phase protein.
21351366 Improving the quality of rheumatoid arthritis patients' education using written informatio 2011 Mar OBJECTIVE: The objective of this study was to evaluate whether the quality of patient education could be improved by using written education materials. METHODS: Seventy-five inpatients with rheumatoid arthritis (RA) were provided with individual education sessions during their inpatient stay. The education sessions were supported with written educational materials. A patient education quality instrument was used to assess the sufficiency and implementation of the education and the readiness of nurses and doctors to deliver the education. A Mann-Whitney U-test and content analysis was used to analyse the data. RESULTS: There was a statistically significant difference in the sufficiency of education concerning the disease, medication and treatment after the revised material was introduced (p < 0.005). The quality of interaction improved significantly during the intervention (p = 0.004). The strengths of the education included individual treatment, two-way interaction, the opportunity to receive patient education and its sufficiency. CONCLUSION: Clear, readable and understandable written education material improved the quality of the education of RA patients in terms of implementation, sufficiency and the readiness of nurses and doctors to deliver the education.
19922831 Absorbed dose profiles for (32)P, (90)Y, (188)Re, (177)Lu, (153)Sm and (169)Er: radionucli 2009 Jul The main objective of this paper was to obtain the absorbed dose profiles for radionuclides of frequent or potential use in radiosynoviortheses. These profiles reveal the absorbed dose per activity of injected radionuclide (Gy/h*MBq) in the synovial membrane and the articular cartilage. The researched radionuclides were (32)P, (90)Y, (188)Re, (177)Lu, (153)Sm and (169)Er. The therapeutic range of each radionuclides in synovial tissue were also calculated. This range determines the synovial thickness that can be sufficiently irradiated and thus successfully treated. The S values for the synovial membrane and articular cartilage were calculated using as a model a cylinder with the source uniformly distributed in its volume. The synovial membrane was simulated varying the radius of the cylinder (from 0.5cm to 9cm) and its height (from 0.01cm to 0.04cm). The area in the base of the cylinder represents different sizes of the synovial surface (small, medium and large joints). The height of the cylinder represents different stages of the progression of the rheumatoid arthritis. The same model was used to simulate the articular cartilage but, the source was uniformly distributed into a cylindrical slab (0.01cm height and 1cm of radius. The results obtained allow the estimation of the dose that will be delivered to the synovial membrane and the articular cartilage for different joint sizes and different stages of progression of the rheumatoid arthritis (RA).
19930661 CTLA4-Ig interacts with cultured synovial macrophages from rheumatoid arthritis patients a 2009 INTRODUCTION: Co-stimulatory signal B7(CD80/CD86):CD28 is needed in order to activate T cells in immune response. Cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4-Ig) binding to the B7 molecules on antigen-presenting cells downregulates this activation and represents a recent biological treatment in rheumatoid arthritis (RA). Objectives of the study were to investigate the presence of the B7.2 (CD86) molecule and its masking by CTLA4-Ig on cultures of both RA synovial macrophages (RA SM), and of macrophages differentiated from THP-1 cells (M). In addition, the anti-inflammatory effects of CTLA4-Ig on co-cultures of RA SM and M with activated T cells were tested. METHODS: All macrophages were co-cultured for 24 hours with activated T cells, without or with CTLA4-Ig (10, 100, 500 microg/ml for 1 hour, 3 hours and overnight, respectively). Immunofluorescence (IF) staining for B7.2, and an analysis of inflammatory cytokine expression (interleukin (IL) -6, tumor necrosis factor (TNF) alpha, IL-1beta, transforming growth factor (TGF) beta) by immunocytochemistry (ICC), western blot (WB) and reverse transcriptase-polymerase chain reaction (RT-PCR) were performed. RESULTS: Macrophages showed intense B7.2 expression. CTLA4-Ig/B7.2 masking was evident for all macrophages, even after only 1 hour of cell culture (range from 10 to 100 microg/ml). ICC of co-cultures showed a dose-dependent decrease in inflammatory cytokines (P < 0.001 for IL-6, TNFalpha, IL-1beta and TGFbeta). Data were confirmed by WB and RT-PCR analysis. CONCLUSIONS: Optimal concentrations of CTLA4-Ig for the CTLA4-Ig/B7.2 masking on activated macrophages were identified and were found to induce significant downregulation in the cell production of IL-6, TNFalpha, IL1-beta and TGFbeta. In conclusion, macrophages would appear to be a sensitive target for CTLA4-Ig treatment in RA.
20473756 The efficacy and safety of rituximab for the treatment of active rheumatoid arthritis: a s 2011 Nov The aims of this study were to assess the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA). The authors surveyed randomized controlled trials (RCTs) that examined the efficacy of rituximab in disease modifying anti-rheumatic drug (DMARD) (including methotrexate [MTX]) or tumor necrosis factor (TNF)-blocker-resistant or intolerant patients with active RA using Medline, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis of RCTs was performed to determine the treatment efficacy and safety outcomes of rituximab (1 course, consisting of two infusions of 1,000 mg each) concomitant with MTX. The three RCTs included 938 DMARD or TNF-blocker-resistant or intolerant RA patients. Follow-up periods ranged from 24 to 48 weeks. American College of Rheumatology response (ACR) 20, ACR50, and ACR70 response rates were significantly higher for the rituximab plus MTX than for placebo controls (primary efficacy outcome, ACR50; risk ratio [RR] 3.648, 95% confidence interval [CI] 2.478-5.369, P < 0.001). For those treated with rituximab, the incidence adverse events of all systems were not higher than in those treated with placebo (RR 1.062, 95% CI 0.912-1.236, P = 0.438). With respect to the number of patients that experienced at least one serious adverse event, no significant difference was observed between patients treated with rituximab and placebo (RR 0.855, 95% CI 0.622-1.174, P = 0.333). A single course of rituximab with concomitant MTX therapy was found to be effective in DMARD or TNF-blocker-resistant or intolerant patients with active RA.
21097801 Indirect comparisons of the efficacy of biological antirheumatic agents in rheumatoid arth 2011 Feb BACKGROUND: The availability of increasing numbers of biological agents for the treatment of rheumatoid arthritis (RA) offers several therapeutic options. While all biologicals have proven effective in trials, very limited direct comparisons are available. The objective of the present work was to compare the efficacy of biologicals (anti-tumour necrosis factor (TNF) agents, rituximab, abatacept, tocilizumab) in patients with RA with active disease and (i) an inadequate response (IR) to methotrexate (IR-MTX), (ii) an IR to anti-TNF agents (IR-anti-TNFs) using indirect comparisons. METHODS: Randomised clinical trials were identified examining the efficacy of a biological agent in RA at 6 months in patients with an IR-MTX or with an IR-anti-TNF. To compare the relative efficacy of biologicals, adjusted indirect comparison meta-analytic methods to estimate the ORs of achieving a 50% improvement according to American College of Rheumatology criteria (ACR50) response at 6 months were used. RESULTS: A total of 18 published trials and 1 abstract were included in the analyses. In IR-MTX, anti-TNFs had the same probability of reaching an ACR50 compared to 'non-anti-TNF biologicals' taken together (OR 1.30, 95 % CI 0.91 to 1.86). However, when compared to specific biological agents, anti-TNFs demonstrated a higher probability of reaching an ACR50 than abatacept (OR 1.52, 95 % CI 1.0 to 2.28), but not in comparison to rituximab and tocilizumab. In IR-anti-TNF, no significant differences existed between rituximab, tocilizumab, abatacept and golimumab. [corrected] CONCLUSIONS: In a meta-analysis of randomised clinical trials of patients with IR-MTX, anti-TNFs demonstrated a higher probability of achieving an ACR50 response than abatacept. In IR-anti-TNF, no difference was found between rituximab, tocimizumab, abatacept and golimumab.
20920694 Outcomes in patients with rheumatoid arthritis and myocardial infarction. 2010 Oct BACKGROUND: Patients with rheumatoid arthritis have an increased risk for accelerated atherosclerosis. It is unknown, however, whether rheumatoid arthritis also increases in-hospital mortality after a myocardial infarction or influences the therapy patients receive. METHODS: A cross-sectional analysis of 1,112,676 patients with myocardial infarction in the 2003-2005 Nationwide Inpatient Sample was performed. RESULTS: Patients with rheumatoid arthritis were 39% more likely to receive medical therapy (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.30-1.49) than interventional therapy. By using logistic regression, we adjusted for confounding variables to determine the effect of rheumatoid arthritis on the selection of therapy and found that rheumatoid arthritis itself was associated with a 38% increased likelihood of undergoing thrombolysis (OR, 1.38; 95% CI, 1.10-1.71) and a 27% increased likelihood of undergoing percutaneous coronary intervention (OR, 1.27; 95% CI, 1.17-1.39). For the primary outcome measure, we determined that patients with rheumatoid arthritis overall had a 24% better in-hospital mortality compared with other patients with a myocardial infarction (OR, 0.76; 95% CI, 0.68-0.86), which was 34% better after adjusting for confounding variables (OR, 0.66; 95% CI, 0.59-0.74). This better in-hospital mortality was seen in patients with rheumatoid arthritis undergoing medical therapy (adjusted OR, 0.67; 95% CI, 0.59-0.75) and percutaneous coronary intervention (adjusted OR, 0.47; 95% CI, 0.32-0.70), but not in patients undergoing thrombolysis or coronary artery bypass grafting. CONCLUSIONS: Among patients with myocardial infarction, rheumatoid arthritis was associated with an increased use of thrombolysis and percutaneous coronary intervention. Moreover, patients with rheumatoid arthritis had an in-hospital survival advantage, particularly those undergoing medical therapy and percutaneous coronary intervention.
19828325 Dose calculation from a D-D-reaction-based BSA for boron neutron capture synovectomy. 2010 Apr Monte Carlo simulations were carried out to calculate dose in a knee phantom from a D-D-reaction-based Beam Shaping Assembly (BSA) for Boron Neutron Capture Synovectomy (BNCS). The BSA consists of a D(d,n)-reaction-based neutron source enclosed inside a polyethylene moderator and graphite reflector. The polyethylene moderator and graphite reflector sizes were optimized to deliver the highest ratio of thermal to fast neutron yield at the knee phantom. Then neutron dose was calculated at various depths in a knee phantom loaded with boron and therapeutic ratios of synovium dose/skin dose and synovium dose/bone dose were determined. Normalized to same boron loading in synovium, the values of the therapeutic ratios obtained in the present study are 12-30 times higher than the published values.
20003323 RANKL inhibition by osteoprotegerin prevents bone loss without affecting local or systemic 2009 INTRODUCTION: Rat adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) feature bone loss and systemic increases in TNFalpha, IL-1beta, and receptor activator of NF-kappaB ligand (RANKL). Anti-IL-1 or anti-TNFalpha therapies consistently reduce inflammation in these models, but systemic bone loss often persists. RANKL inhibition consistently prevents bone loss in both models without reducing joint inflammation. Effects of these therapies on systemic markers of bone turnover and inflammation have not been directly compared. METHODS: Lewis rats with established AIA or CIA were treated for 10 days (from day 4 post onset) with either PBS (Veh), TNFalpha inhibitor (pegsunercept), IL-1 inhibitor (anakinra), or RANKL inhibitor (osteoprotegerin (OPG)-Fc). Local inflammation was evaluated by monitoring hind paw swelling. Bone mineral density (BMD) of paws and lumbar vertebrae was assessed by dual X-ray absorptiometry. Markers and mediators of bone resorption (RANKL, tartrate-resistant acid phosphatase 5b (TRACP 5B)) and inflammation (prostaglandin E2 (PGE2), acute-phase protein alpha-1-acid glycoprotein (alpha1AGP), multiple cytokines) were measured in serum (day 14 post onset). RESULTS: Arthritis progression significantly increased paw swelling and ankle and vertebral BMD loss. Anti-TNFalpha reduced paw swelling in both models, and reduced ankle BMD loss in AIA rats. Anti-IL-1 decreased paw swelling in CIA rats, and reduced ankle BMD loss in both models. Anti-TNFalpha and anti-IL-1 failed to prevent vertebral BMD loss in either model. OPG-Fc reduced BMD loss in ankles and vertebrae in both models, but had no effect on paw swelling. Serum RANKL was elevated in AIA-Veh and CIA-Veh rats. While antiTNFalpha and anti-IL-1 partially normalized serum RANKL without any changes in serum TRACP 5B, OPG-Fc treatment reduced serum TRACP 5B by over 90% in both CIA and AIA rats. CIA-Veh and AIA-Veh rats had increased serum alpha1AGP, IL-1beta, IL-8 and chemokine (C-C motif) ligand 2 (CCL2), and AIA-Veh rats also had significantly greater serum PGE2, TNFalpha and IL-17. Anti-TNFalpha reduced systemic alpha1AGP, CCL2 and PGE2 in AIA rats, while anti-IL-1 decreased systemic alpha1AGP, IL-8 and PGE2. In contrast, RANKL inhibition by OPG-Fc did not lessen systemic cytokine levels in either model. CONCLUSIONS: Anti-TNFalpha or anti-IL-1 therapy inhibited parameters of local and systemic inflammation, and partially reduced local but not systemic bone loss in AIA and CIA rats. RANKL inhibition prevented local and systemic bone loss without significantly inhibiting local or systemic inflammatory parameters.
19066175 Definition of arthritis candidate risk genes by combining rat linkage-mapping results with 2009 Dec OBJECTIVE: To define genomic regions that link to rat arthritis and to determine the potential association with rheumatoid arthritis (RA) of the corresponding human genomic regions. METHODS: Advanced intercross lines (AIL) between arthritis susceptible DA rats and arthritis resistant PVG.1AV1 rats were injected with differently arthritogenic oils to achieve an experimental situation with substantial phenotypic variation in the rat study population. Genotyping of microsatellite markers was performed over genomic regions with documented impact on arthritis, located on rat chromosomes 4, 10 and 12. Linkage between genotypes and phenotypes were determined by R/quantitative trait loci (QTL). Potential association with RA of single nucleotide polymorphisms (SNPs) in homologous human chromosome regions was evaluated from public Wellcome Trust Case Control Consortium (WTCCC) data derived from 2000 cases and 3000 controls. RESULTS: A high frequency of arthritis (57%) was recorded in 422 rats injected with pristane. Maximum linkage to pristane-induced arthritis occurred less than 130 kb from the known genetic arthritis determinants Ncf1 and APLEC, demonstrating remarkable mapping precision. Five novel quantitative trait loci were mapped on rat chromosomes 4 and 10, with narrow confidence intervals. Some exerted sex-biased effects and some were linked to chronic arthritis. Human homologous genomic regions contain loci where multiple nearby SNPs associate nominally with RA (eg, at the genes encoding protein kinase Calpha and interleukin 17 receptor alpha). CONCLUSIONS: High-resolution mapping in AIL populations defines limited sets of candidate risk genes, some of which appear also to associate with RA and thus may give clues to evolutionarily conserved pathways that lead to arthritis.
19895848 IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population 2010 Jan 4 Interleukin-17-producing CD4(+) T cells (Th17 cells) are the dominant pathogenic cellular component in autoimmune inflammatory diseases, including autoimmune arthritis. IL-10 promotes the generation of Foxp3(+) regulatory T cells via the IL-10 receptor signal. The objective of this study was to examine whether IL-10, which acts as an anti-inflammatory cytokine, has a suppressive effect on the activation of human Th17 cells. Expression of IL-17 and IL-10 was examined immunohistochemically in tissue obtained from rheumatoid arthritis patients. Human peripheral blood CD4(+) T cells were isolated and cultured under various stimulatory conditions. Th17 cells and regulatory T (Treg) cells were detected by flow cytometry. The gene expression of related cytokines and transcription factors were assessed by ELISA and RT-PCR. IL-17 was overexpressed in rheumatoid arthritis patients. IL-10 treatment significantly decreased the numbers of IL-17-producing and RORc-expressing cells among human CD4(+) T cells that had been activated in vitro by Th17-differentiating conditions in autoimmune arthritis patients. IL-10 induced Foxp3(+) regulatory T cells in the human CD4(+) T cell population. Our results demonstrate that IL-17 is overexpressed in autoimmune disease patients and that IL-10 suppresses IL-17 expression. IL-10 may be useful in the treatment of autoimmune diseases.
20039434 Inhibition of synovial hyperplasia, rheumatoid T cell activation, and experimental arthrit 2010 Jan OBJECTIVE: To investigate whether sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables such as broccoli, regulates synoviocyte hyperplasia and T cell activation in rheumatoid arthritis (RA). METHODS: Synoviocyte survival was assessed by MTT assay. The levels of Bcl-2, Bax, p53, and pAkt were determined by Western blot analysis. Cytokine concentrations in culture supernatants from mononuclear cells were analyzed by enzyme-linked immunosorbent assay. The in vivo effects of SFN were examined in mice with experimentally induced arthritis. RESULTS: SFN induced synoviocyte apoptosis by modulating the expression of Bcl-2/Bax, p53, and pAkt. In addition, nonapoptotic doses of SFN inhibited T cell proliferation and the production of interleukin-17 (IL-17) and tumor necrosis factor alpha (TNFalpha) by RA CD4+ T cells stimulated with anti-CD3 antibody. Anti-CD3 antibody-induced increases in the expression of retinoic acid-related orphan receptor gammat and T-bet were also repressed by SFN. Moreover, the intraperitoneal administration of SFN to mice suppressed the clinical severity of arthritis induced by injection of type II collagen (CII), the anti-CII antibody levels, and the T cell responses to CII. The production of IL-17, TNFalpha, IL-6, and interferon-gamma by lymph node cells and spleen cells from these mice was markedly reduced by treatment with SFN. Anti-CII antibody-induced arthritis in mice was also alleviated by SFN injection. CONCLUSION: SFN was found to inhibit synovial hyperplasia, activated T cell proliferation, and the production of IL-17 and TNFalpha by rheumatoid T cells in vitro. The antiarthritic and immune regulatory effects of SFN, which were confirmed in vivo, suggest that SFN may offer a possible treatment option for RA.
19411000 Total elbow arthroplasty: surgical technique. 2009 May Implant arthroplasty about the elbow using custom metal components for the distal humerus and proximal ulna was developed in the 1960s. Before this time, the only salvage procedures available for destructive joint disease about the elbow were resection arthroplasty, fascial interposition arthroplasty, or elbow arthrodesis. Today, many total elbow arthroplasty designs are available and used throughout the world. The Coonrad-Morrey total elbow prosthesis (Zimmer, Warsaw, IN) is the most widely used implant for elbow arthroplasty in the United States and has been chosen for discussion in this surgical technique article.
20173385 Cellular mechanisms of TNF function in models of inflammation and autoimmunity. 2010 The TNF/TNF receptor (TNFR) system has a prominent role in the pathogenesis of chronic inflammatory and autoimmune disorders. Extensive research in animal models with deregulated TNF expression has documented that TNF may initiate or sustain inflammatory pathology, while at the same time may exert immunomodulatory or disease-suppressive activities. The TNF/TNFR system encompassing both the soluble and the transmembrane form of TNF with differential biological activities, as well as the differential usage of its receptors, mediating distinct functions, appears to confer complexity but also specificity in the action of TNF. The inherent complexity in TNF-mediated pathophysiology highlights the requirement to address the role of TNF taking into account both proinflammatory tissue-damaging and immunomodulatory functions in a cellular and receptor-specific manner. In this review, we discuss our current understanding of the involvement of TNF in chronic inflammation and autoimmunity, focusing on TNF-mediated cellular pathways leading to the pathogenesis or progression of joint and intestinal inflammatory pathology. Knowledge of the mechanisms by which TNF either initiates or contributes to disease pathology is fundamentally required for the design of safe and effective anti-TNF/TNFR therapies for human inflammatory and autoimmune disorders.
20091076 Anti-agalactosyl IgG antibodies in Thai patients with rheumatoid arthritis, systemic lupus 2010 Mar This study was performed to determine the prevalence of anti-agalactosyl IgG antibodies in Thai patients with RA, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and determine the sensitivity and specificity of anti-agalactosyl IgG antibodies in the diagnosis of RA in comparison with IgM-rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Serum samples were obtained from 100 patients with RA, 50 cases of SLE, 50 cases of SSc, and 100 healthy controls and analyzed for the presence of anti-agalactosyl IgG antibodies, IgM-RF and anti-CCP antibodies. A serum value greater than mean + 2 standard deviation of normal value of anti-agalactosyl IgG antibodies and anti-CCP antibodies was considered positive. The prevalence of anti-agalactosyl IgG antibodies in RA, SLE, and SSc patients was 88.0%, 14.0%, and 12.0%, respectively. The serum level of anti-agalactosyl IgG antibodies in patients with RA (227.10 +/- 353.64 AU/mL) was significantly higher than those in SLE (11.84 +/- 52.04 AU/mL), SSc (18.85 +/- 99.60 AU/mL), and healthy controls (2.14 +/- 1.97 AU/mL), (p < 0.001). There was a good correlation between the log serum level of anti-agalactosyl IgG antibodies and IgM-RF (r = 0.92, p < 0.001), anti-CCP antibodies and IgM-RF (r = 0.49, p < 0.001), and anti-agalactosyl IgG antibodies and anti-CCP antibodies (r = 0.55, p < 0.001). The sensitivity and specificity in the diagnosis of RA was 88.00% and 96.00% for anti-agalactosyl IgG antibodies, 90.00% and 99.00% for anti-CCP antibodies, and 91.00% and 95.00% for IgM-RF, respectively. The serum level of anti-agalactosyl IgG antibodies was significantly higher in RA than in SLE, SSc, and healthy controls. There was a good correlation between serum levels of anti-agalactosyl IgG antibodies, anti-CCP antibodies, and IgM-RF. These three tests had comparable sensitivity and specificity.
19410984 A multicenter clinical trial in rheumatoid arthritis comparing silicone metacarpophalangea 2009 May PURPOSE: Metacarpophalangeal (MCP) joint deformities caused by rheumatoid arthritis can be treated using silicone metacarpophalangeal joint arthroplasty (SMPA). There is no consensus as to whether this surgical procedure is beneficial. The purpose of the study was to prospectively compare outcomes for a surgical and a nonsurgical cohort of rheumatoid arthritis patients. METHODS: The prospective study was conducted from January 2004 to May 2008 at 3 referral centers in the United States and England. Over a 3-year period, 70 surgical and 93 nonsurgical patients were recruited. One year data are available for 45 cases and 72 controls. All patients had severe ulnar drift and/or extensor lag of the fingers at the MCP joints. The patients all had 1-year follow-up evaluations. Patients could elect to have SMPA and medical therapy or medical therapy alone. Outcomes included the Michigan Hand Outcomes Questionnaire (MHQ), Arthritis Impact Measurement Scales, grip and pinch strength, Jebson-Taylor test, and ulnar deviation and extensor lag measurements at the MCP joints. RESULTS: There was no difference in the mean age for the surgical group (60) when compared to the nonsurgical group (62). There was also no significant difference in race, education, and income between the 2 groups. At 1-year follow-up, the mean overall MHQ score showed significant improvement in the surgical group but no change in the nonsurgical group, despite worse MHQ function at baseline in the surgical group. Ulnar deviation and extensor lag improved significantly in the surgical group, but the mean Arthritis Impact Measurement Scales scores and grip and pinch strength showed no significant improvement. CONCLUSIONS: This prospective study demonstrated significant improvement for RA patients with poor baseline functioning treated with SMPA. The nonsurgical group had better MHQ scores at baseline, and their function did not deteriorate during the 1-year follow-up interval.
19698242 [Identification of mesenchymal stem cells derived from rheumatoid arthritis synovial fluid 2009 Aug This study was purposed to investigate the influence of inflammatory microenvironment on mesenchymal stem cells (MSCs) and regulatory effect of MSCs on osteoblast formation. The MSCs were isolated from synovial fluid of patients with rheumatoid arthritis (RASF-MSCs) and were cultured, the immunotypes of RASF-MSCs were detected by flow cytometry, the ability to differentiate RASF-MSCs into osteoblasts and adipocytes was determined by means of osteogenic and adipogenic induction, the regulatory effect of RASF-MSCs on osteoblast formation was assayed by co-culturing RASF-MSCs whth CD14(+) monocytes and in situ tartrate-resistant acid phosphatase staining. The results showed that RASF-MSCs highly expressed CD105, CD73, CD29, CD44, CD166 and HLA-ABC. Meanwhile, they lowly expressed CD34, CD45, CD31, HLA-DR, CD80 and CD86. However, RASF-MSCs decreased multi-differentiation capability as compared with BM-MSCs. More interestingly, RASF-MSC significantly promoted osteoclasts formation (p < 0.05) when co-cultured with monocytes. It is concluded that MSCs from rheumatoid arthritis synovial fluid exert typical MSC phenotypes but displayed decline of multi-differentiation capability. RASF-MSCs especially show promoting effect on osteoclastogenesis. The findings of this study may contribute to the understanding biological behavior of MSCs in pathological microenvironment.