Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
20646075 The influence of regulatory T cells and diurnal hormone rhythms on T helper cell activity. 2010 Dec Symptoms of diseases such as rheumatoid arthritis, which is T helper 1 (Th1) dependent, and asthma, which is T helper 2 (Th2) dependent, are influenced by diurnal rhythms and natural regulatory T cells (nTreg). However, the mechanisms responsible for the diurnal rhythm of disease activity have not been identified and it is unclear whether nTreg activity is diurnal rhythm-dependent. We therefore investigated whether a 24-hr diurnal cycle affected the ability of various helper T-cell populations to generate immunomodulatory and pro-inflammatory cytokines, as well as its suppression by nTreg cells. Using a within-subject crossover design, sleep versus continuous wakefulness was compared over a 24-hr period in healthy young volunteers under defined environmental conditions. Venous blood was drawn periodically every 5 hr and the function of T cells was explored in vitro. We demonstrated that interleukin (IL)-2, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and IL-10 secretion by naïve CD4(+) T cells follows a diurnal rhythm. Furthermore, multiple regression analysis, as well as subsequent in vitro experiments, suggested that serum levels of cortisol and prolactin are part of the underlying mechanism. Additionally, we observed that nTreg suppressed the secretion of IFN-γ, IL-2 and TNF-α, but not the secretion of IL-4, IL-6, IL-10 and IL-17A. However, the abrogation of IL-2 release was reversed upon inhibiting CD25 on nTreg. Highly purified nTreg secreted IL-6, IL-10 and IL-17A, but not IL-2, IL-4, IFN-γ or TNF-α. Taken together, our results demonstrate that hormones and nTreg modulate the diurnal rhythm of T helper cell activity.
20676645 White cells count in smokers affected by rheumatic diseases. 2012 Jan Evidence shows that tobacco smoking interacts with development of rheumatic diseases. Increase in white cells count (leukocytosis) is frequently present, and in smokers, it is considered a biomarker of cardiovascular risk. Aim of the study is to evaluate this biomarker in smokers with rheumatic diagnosis. We carried out an observational study on 115 rheumatic outpatients (26 men and 89 women) divided into two groups according to their smoking habit: one composed of 56 smokers, the other of 59 not smokers. Diagnosis and common routinary clinical parameters were collected. In the total sample, smokers were 48.69%. Most common diagnosis was osteoarthritis (OA) (40.87% of the total); smokers in OA women were 36.11%, smokers in OA men were 54.55%. Second most common diagnosis was rheumatoid arthritis (RA) (23.48% of the total); smokers in RA women were 40.91%; smokers in RA men were 80%. OA smokers showed a significant increase (P < 0.05) in white cells count when compared with OA not smokers. Between RA smokers and not smokers, any clinical difference was found. RA subjects following regular pharmacological treatment in the last 2 months were 84.61%. OA patients treated with drugs in the last 2 months were only 22.2%. Results seem to confirm that smoking habit may influence the development as well as gender distribution of rheumatic diseases. They show also that in absence of pharmacological treatment in smokers affected by OA leukocytosis (biomarker of cardiovascular risk) is observed.
20538198 Self-report as an indicator of incident disease. 2010 Jul PURPOSE: Epidemiological studies use self-reports from repeated surveys to ascertain incident disease. However, the accuracy of such measurements remains unknown, as validity studies have typically relied on data from prevalent, rather than incident, disease. This study examined the validity of self-reports in the detection of new-onset disease with measurements at baseline and follow-up conditions. METHODS: We conducted a prospective cohort study of 34,616 Finnish public-sector employees. Data from self-reported, physician-diagnosed diseases from two surveys approximately 4 years apart were compared with corresponding records in comprehensive national health registers used as the validity criterion. RESULTS: There was a considerable degree of misclassification for self-reports as a measure of incident disease. The specificity of self-reports was equally high for the prevalent and incident diseases (range, 93%-99%), but the sensitivity of self-reports was considerably lower for incident than for prevalent diseases: hypertension (55% vs. 86%), diabetes (62% vs. 96%), asthma (63% vs. 91%), coronary heart disease (62% vs. 78%), and rheumatoid arthritis (63% vs. 83%). CONCLUSIONS: This study suggests that the sensitivity of self-reports is substantially worse for incident than for prevalent diseases. Results from studies on self-reported incident chronic conditions should be interpreted with caution.
20392239 Inhibition of antigen presentation and T cell costimulation blocks PTH-induced bone loss. 2010 Mar T cells are required for continuous parathyroid hormone (cPTH) treatment to induce bone loss as they sensitize stromal cells to PTH through CD40 ligand (CD40L), a surface molecule of activated T cells. Since CD40L expression is a feature of activated T cells, we investigated whether antigen (Ag)-mediated T cell activation is required for PTH to exert its catabolic activity. We report that inhibition of Ag presentation through silencing of either class I or class II MHC-T cell receptor (TCR) interaction prevents the cortical bone loss induced by in vivo cPTH treatment. We also show that the bone loss and the stimulation of bone resorption induced by cPTH treatment are prevented by CTLA4-Ig, an inhibitor of T cell costimulation approved for the treatment of rheumatoid arthritis. Since inhibition of antigen-driven T cell activation by blockade of either TCR signaling or T cell costimulation is sufficient to silence the catabolic activity of cPTH, antigen-presenting cells and T lymphocyte interactions therefore play a critical role in the mechanism of action of PTH.
19333898 Fostamatinib, a Syk inhibitor prodrug for the treatment of inflammatory diseases. 2009 Mar Rigel Pharmaceuticals Inc is developing fostamatinib, a prodrug of the spleen tyrosine kinase (Syk) inhibitor R-406, for the potential treatment of autoimmune diseases such as rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura (ITP) and B-cell lymphomas. Syk is a key mediator of Fc and B-cell receptor signaling in inflammatory cells, such as B-cells, mast cells, macrophages and neutrophils. Preclinical studies of R-406 or fostamatinib demonstrated a significant reduction in major inflammatory mediators such as TNFalpha, IL-1, IL-6 and IL-18, leading to reduced inflammation and bone degradation in models of RA. In a phase II clinical trial, fostamatinib treatment effectively improved American College of Rheumatology response rates in patients with RA. Preclinical studies and phase II trials also suggested the potential of using fostamatinib for the treatment of ITP and B-cell lymphomas, by increasing platelet counts and inducing response rates, respectively. Fostamatinib is orally bioavailable and was well tolerated in phase I and II trials, with the most common side effect being gastrointestinal symptoms. At the time of publication, phase II trials for fostamatinib were ongoing in patients with RA, ITP and B-cell lymphomas. The Syk inhibitor appears to be a promising therapeutic for immunological diseases, but further data are required to establish the efficacy and long-term safety of the drug in humans.
20220768 A candidate gene study of CLEC16A does not provide evidence of association with risk for a 2010 Sep CLEC16A, a putative immunoreceptor, was recently established as a susceptibility locus for type I diabetes and multiple sclerosis. Subsequently, associations between CLEC16A and rheumatoid arthritis (RA), Addison's disease and Crohn's disease have been reported. A large comprehensive and independent investigation of CLEC16A variation in RA was pursued. This study tested 251 CLEC16A single-nucleotide polymorphisms in 2542 RA cases (85% anti-cyclic citrullinated peptide (anti-CCP) positive) and 2210 controls (N=4752). All individuals were of European ancestry, as determined by ancestry informative genetic markers. No evidence for significant association between CLEC16A variation and RA was observed. This is the first study to fully characterize common genetic variation in CLEC16A including assessment of haplotypes and gender-specific effects. The previously reported association between RA and rs6498169 was not replicated. Results show that CLEC16A does not have a prominent function in susceptibility to anti-CCP-positive RA.
19317607 Effectiveness and safety of etanercept in subjects with RA who have failed infliximab ther 2009 May BACKGROUND AND OBJECTIVE: Tumor necrosis factor (TNF) antagonists, including etanercept (a soluble TNF receptor) and infliximab (an anti-TNF monoclonal antibody) are used in the treatment of patients with rheumatoid arthritis (RA). The purpose of this study was to evaluate the effectiveness and safety of 50 mg etanercept weekly in subjects with RA who have failed infliximab therapy. METHODS: This phase 4, multicenter, open-label, single-arm, 16-week observational study enrolled subjects who had experienced primary (failure to achieve an initial response) or secondary (failure to maintain an initial response) infliximab failures. Effectiveness was measured using European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) response criteria and laboratory assessments were used to evaluate levels of inflammation, lymphotoxin alpha, drug concentrations, and antibodies to infliximab. Safety endpoints included incidence of serious adverse events. CLINICAL TRIAL REGISTRATION: This trial was registered under U.S. National Institutes of Health ClinicalTrials.gov identifier NCT00099554. RESULTS: At week 16, over half (62%; 95% CI = 55, 69) of all subjects in the trial achieved a good or moderate EULAR response (DAS28) with etanercept. Using ACR criteria, after 16 weeks of etanercept therapy, 45% (95% CI = 38, 52) of all subjects had achieved an ACR20 response. Benefits were noted in tender and swollen joint counts, subject and physician global assessments, joint pain, and the Health Assessment Questionnaire. Outcomes were similar between subjects with primary and secondary infliximab failures. Levels of lymphotoxin alpha did not appear to affect response to etanercept. Potential limitations included the lack of a washout period, short duration of the trial, and the number of subjects who did not receive all doses of etanercept. CONCLUSION: In this open-label, uncontrolled study, subjects with moderate to severe RA who failed to respond or who lost their initial response to infliximab safely benefited from receiving etanercept.
20117312 Clinical research in hand surgery. 2010 Jan Clinical research designed to enhance the quality of health care has always received a great deal of national attention. Outcomes studies, clinical trials, and evidence-based research are key components of clinical research that have advanced the field of hand surgery. The purpose of the Weiland Award is to encourage innovations and progress in clinical research in hand surgery for the betterment of patients and to promote hand surgery's visibility in American medicine. This article will highlight my efforts in clinical research through 3 specific research themes: (1) outcomes research, (2) economic analysis, and (3) evidence-based research and quality assessment in health care.
19324522 Sex hormones modulate the effects of Leflunomide on cytokine production by cultures of dif 2009 May Immune response is greater in females than in males and lymphocytes/monocytes from female subjects (or tested in vitro with estrogens) show higher immune/inflammatory reactivity. In order to test in vitro the interactions between 17beta-estradiol (E2--10(-9) M), testosterone (T--10(-8) M) and the antiproliferative/immune suppressive drug Leflunomide metabolite A77 1726 (LEF-M--30 microM) employed in rheumatoid arthritis (RA), their combined effects were evaluated on inflammatory cytokine (CK) expression/production in cultures of differentiated macrophages (M) (from activated THP-1 monocytes) and primary cultures of RA synovial macrophages (SM). TNFalpha, IL-6 and TGFbeta were detected by immunocytochemistry (ICC), Western blot analysis (WB) and reverse transcriptase-polymerase chain reaction (RT-PCR). The ICC, WB and RT-PCR showed a significant down-regulation induced by LEF-M on CK expression by cultured M when compared to untreated cells (IL-6 p < 0.01, TNFalpha p < 0.001, TGFbeta p < 0.01). At ICC analysis E2 increased CK expression, whereas T decreased the expression, confirmed by WB and RT-PCR (range between p < 0.05 and p < 0.001). LEF-M treatment significantly downregulated the CK expression in E2/T treated M: the effect was more significant in LEF-M plus T-treated cells versus controls (range between p < 0.01 and p < 0.001). Concerning the RA SM, the results were replicated (range between p < 0.05 and p < 0.001). E2 seems to contrast, but T seems to synergize the LEF-M activity. Results might support a stronger therapeutical efficacy, at least for LEF, in male RA patients, as already reported by clinical evidences.
19785857 [Methotrexate: safe if prescribed correctly]. 2009 Methotrexate (MTX) is an effective medicine that can be safely used for the treatment of rheumatic arthritis and severe cases of psoriasis. For nearly all indications MTX is prescribed as a weekly dose. As a result of prescription errors, miscommunication, failing pharmacovigilance and lack of knowledge, fatal incidents have occurred due to prescriptions for a dosage once daily instead of once weekly. To prevent such incidences in the future, a balanced automatic pharmacovigilance, clear instructions for the use of MTX on the prescription and good patient information are needed.
20952464 Increased prevalence of metabolic syndrome associated with rheumatoid arthritis in patient 2011 Jan OBJECTIVE: to examine whether patients with rheumatoid arthritis (RA) with no overt cardiovascular disease (CVD) have a higher prevalence of metabolic syndrome (MetS) than subjects without RA or CVD. We also examined whether RA disease characteristics are associated with the presence of MetS in RA patients without CVD. METHODS: subjects from a population-based cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA between January 1, 1980, and December 31, 2007, were compared to non-RA subjects from the same population. All subjects with any history of CVD were excluded. Waist circumference, body mass index (BMI), and blood pressure were measured during the study visit. Data on CVD, lipids, and glucose measures were ascertained from medical records. MetS was defined using NCEP/ATP III criteria. Differences between the 2 cohorts were examined using logistic regression models adjusted for age and sex. RESULTS: the study included 232 RA subjects without CVD and 1241 non-RA subjects without CVD. RA patients were significantly more likely to have increased waist circumference and elevated blood pressure than non-RA subjects, even though BMI was similar in both groups. Significantly more RA patients were classified as having MetS. In RA patients, MetS was associated with Health Assessment Questionnaire Disability Index, large-joint swelling, and uric acid levels, but not with C-reactive protein or RA therapies. CONCLUSION: among subjects with no history of CVD, patients with RA are more likely to have MetS than non-RA subjects. MetS in patients with RA was associated with some measures of disease activity.
19474812 Therapeutic silencing of an endogenous gene by siRNA cream in an arthritis model mouse. 2009 Aug Recent advances of biotechnology have laid the groundwork for potent and specific molecular-targeting therapies including RNA interference. The largest remaining hurdle for widespread use of this technology in skin is an effective delivery system. Here, we demonstrate an effective topical delivery system using a cream formulation containing a small-interfering RNA (siRNA) that specifically targets osteopontin (OPN). OPN is a validated target in numerous inflammatory diseases, including rheumatoid arthritis (RA). The siRNA targeting OPN was incorporated into a cream formulation GeneCream that penetrates the stratum corneum, depositing siRNA in the epidermis, dermis, and to a lesser extent, subcutaneous tissue. In addition, when the OPN siRNA cream was topically applied to the skin of a collagen antibody-induced RA mouse model, the siRNA cream prevented the occurrence of severe, irreversible damage to bone and cartilage. Thus, the siRNA cream provides effective delivery of active OPN siRNA, suggesting this formulation may represent a platform technology for delivery of siRNAs for treating various disorders including RA.
19221398 Chromosomal region 16p13: further evidence of increased predisposition to immune diseases. 2010 Jan OBJECTIVE: Genome-wide studies have identified the chromosomal region 16p13 in the susceptibility to type 1 diabetes (T1D) and multiple sclerosis (MS). This region includes the CLEC16A/KIAA0350 gene and an adjacent gene, MHC2TA (MHC class II transactivator), previously associated with susceptibility to MS and rheumatoid arthritis (RA). The role of CLEC16A polymorphisms in the pathogenesis of T1D, MS and RA and its relationship with the association reported with a MHC2TA haplotype were investigated. METHODS: CLEC16A (rs2903692/rs6498169/rs11074956) polymorphisms were analysed in 435 patients with MS, 316 with T1D and 600 with RA and in 550 ethnically matched controls. The MHC2TA rs3087456G/rs4774C risk haplotype was studied in an independent RA cohort. RESULTS: rs2903692 conferred a protective effect on patients with T1D, MS and RA. The described association of rs6498169 with MS was replicated in MS and RA cohorts. The effect of the MHC2TA rs3087456G/rs4774C haplotype on RA susceptibility was confirmed, and the haplotype was found to be in negative linkage disequilibrium with the CLEC16A rs2903692A/rs6498169A haplotype. CONCLUSIONS: Associations of CLEC16A polymorphisms with T1D and MS were successfully replicated in a Spanish population. A novel association of rs6498169 with a predisposition to RA was described which is consistent with previous MHC2TA results. These data provide evidence for the influence of variants within this chromosomal region on the development of complex diseases.
21155991 Older age of rheumatoid arthritis onset is associated with higher activation status of per 2011 Feb Rheumatoid arthritis (RA) is a chronic inflammatory disease, with a clinical manifestation both systemic and in joints. It has been suggested that age at disease onset and/or patients' age have influence on disease activity and clinical outcome. The reasons for the different course of RA in older people are not known; however, the activation status of peripheral blood lymphocytes could be responsible. Our aim was to relate expression of activation markers in peripheral blood CD4(+) T cells of RA patients with patients' age and/or onset age and disease activity measured by DAS28. Seventy RA patients were included into the immunological study. Two separation criteria were performed: based on age of RA onset and on the biological age of patients. We examined different activation markers, CD69, CD25, CD95 and human leucocyte antigen D-related (HLA-DR), on the CD4(+) T cell surface. Division of RA patients in 10-year intervals at 40, 50 and 60 years revealed that RA patients with later disease onset were characterized by higher DAS28. This phenomenon was not limited to the division at 60 years of age but, surprisingly, the major differences were found for the 40-year onset division. Analysis of all four components of DAS28 revealed that disease activity in older disease onset was dependent on all components. Older-onset RA patients had a higher percentage of CD4(+) CD25(+) and CD4(+) CD95(+) T cells. Summarizing the major differences in DAS28 and activation status of CD4(+) T cells observed for onset of disease at 40 years seems to be the most informative about the immunological status of RA patients.
21031267 Ethyl acetate fraction from Cudrania tricuspidata inhibits IL-1β-induced rheumatoid synov 2010 OBJECTIVES: The objective of this study is to determine the effects of Ethyl acetate fraction from Cudrania tricuspidata (EACT) on the interleukin-1b (IL-1b)-induced proliferation of rheumatoid synovial fibroblasts (RASFs) and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) and prostaglandin E2 (PGE2) by RASFs. MATERIALS AND METHODS: The proliferation of RASFs was evaluated with CCK-8 reagent in the presence of IL-1b with/without EACT. The expression of MMPs, TIMP-1, COXs, PGE2 and intracellular MAPK signalings, including p-ERK, p-p38, p-JNK and NF-kB were examined by immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and ELISA in conditions as described above. RESULTS: EACT inhibits IL-1β-induced proliferation of RASFs and MMP-1, 3, COX-2 mRNA and protein expression, PGE2 production induced with IL-1b. EACT also inhibits the phosphorylation of ERK-1/2, p38, JNK and activation of NF-kB by IL-1b. CONCLUSIONS: These results suggest that EACT might be involved in synovial fibroblast proliferation and MMPs, COX-2, and PGE2 production, which are involved in joint destruction in rheumatoid arthritis (RA), indicating that this might be a new therapeutic modality for management of rheumatoid arthritis.
19444449 Altered T-cell subtypes in spondyloarthritis, rheumatoid arthritis and polymyalgia rheumat 2010 Jan The objective of the present study was to assess the prevalences of naive, memory, memory/effector, regulatory and activated T-cells in peripheral blood (PB) and synovial fluid (SF) of patients with spondyloarthritis (SpA), rheumatoid arthritis (RA), polymyalgia rheumatica/giant cell arteritis (PMR/GCA) and healthy controls (HC). Twenty-two patients with SpA, 15 patients with RA, 38 patients with PMR/GCA and 17 HC were prospectively enrolled. The expression of differentiation and activation markers (CD3, CD4, CD8, CD25, CD28, CD45RA, CD45RO) characterizing T-cell subsets were analyzed by flow cytometry. The frequency of CD3(+)CD4(+)CD28(-) memory/effector T-cells was increased in PB of patients with SpA (median 1.1%, range 0.1-69.6), RA (2.5%, 0-42.9) and PMR/GCA (2.7%, 0-49.5) when compared with HC (0.7%, 0-38.0) and tended to be higher in SF of SpA patients (4.5%, 0.2-7.2, P = 0.084). CD28(+)CD45RA(+)CD4(+) (9.6%, 4.1-10.3) and CD28(+)CD45RA(+)CD8(+) naive T-cells (15.0%, 12.9-26.2) were reduced and CD28(+)CD45RO(+)CD4(+) (93.5%, 51.0-99.0), CD28(+)CD45RO(+)CD8(+) memory (81.2%, 38.9-83.5), CD8(+)CD25(+) activated T-cells (10.9%, 2.7-13.8) and CD4(+)CD25(hi) TREGs (10.2%, 7.0-13.3) were increased in SF compared to PB (P < 0.05 each). These findings demonstrate altered T-cell subsets in patients with immune-mediated disease, particularly at sites of inflammation.
20195727 Increased extracellular survivin in the synovial fluid of rheumatoid arthritis patients: f 2010 Dec Survivin belongs to the family of inhibitor of apoptosis proteins and plays an important role in the hyperplastic growth of tissues and tumors. In this study, we assessed the expression of survivin in rheumatoid synovial fluids (SF) and synovial tissues (ST) of rheumatoid arthritis (RA) patients in order to investigate the role of extracellular survivin in the pathogenesis of RA. The survivin level from SF was significantly higher in RA patients (n = 38) than in osteoarthritis patients (n = 18; 10.68 ± 2.76 vs. 1.0 ± 0.56 pg/ml, p = 0.02). In addition, SF survivin level was higher in erosive RA patients (n = 23) than in non-erosive RA patients (n = 15; 15.26 ± 4.26 vs. 4.47 ± 1.12 pg/ml, p = 0.05). SF survivin level in RA was positively correlated with disease activity score 28, but did not reach statistical significance (r = 0.309, p = 0.07). RA SF survivin level was also positively correlated with peripheral blood leukocyte counts (r = 0.443, p = 0.005). The immunohistochemical staining and Western blot analysis revealed survivin expression in the ST and fibroblast-like synoviocytes of RA patients, respectively. These findings suggest that extracellular survivin may be produced from rheumatoid FLS and may play an important role in the destructive RA process.
19327234 Factors determining a DMARD initiation in early inflammatory arthritis patients. The ESPOI 2009 Jan BACKGROUND: To describe the rate and timing of DMARD start in patients with early inflammatory arthritis in France, and to determine the factors leading to this treatment start. METHODS: The ESPOIR cohort study collects data on patients presenting with early arthritis. Baseline characteristics were assessed, and Cox regression analysis was performed to estimate the likelihood of starting DMARD treatment over time, adjusting for patient-, disease- and physician characteristics. RESULTS: Of the 775 analysed patients, 598 (77.2%) received at least 1 DMARD during the follow-up period, after a median time of 4.0 months. In general, a higher tender joint count, involvement of the hands, involvement of more than 3 joint groups, presence of abnormal CRP-levels or CCP-antibodies significantly increased the likelihood of being treated (p<0.01 for all determinants), as well as a positive result on the bilateral foot-squeeze test (p<0.04). In addition, a significant hetero-geneity in therapeutic strategy across the 14 tested French regions was found: adjusted hazard ratios for DMARD start ranged from 1 to 2.15 (p<0.01), depending on the region where a patient was followed. For anti-CCP test and swollen joint count we demonstrated a statistically significant interaction with geographic region, implying that these tests are interpreted differently across regions. The same factors that increased the likelihood to start a DMARD were related to an earlier start. CONCLUSION: Rate and timing of treatment start with DMARDs in patients with early inflammatory arthritis in France is determined by well known clinical and biochemical variables. Apart from these variables, however, unknown and intangible factors that seem to cluster geographically are responsible for important variations in practice performance.
19821388 Dynamic exercise programs (aerobic capacity and/or muscle strength training) in patients w 2009 Oct 7 BACKGROUND: An up-to-date overview of the effectiveness and safety of dynamic exercise therapy (exercise therapy with a sufficient intensity, duration, and frequency to establish improvement in aerobic capacity and/or muscle strength) is lacking. OBJECTIVES: To assess the effectiveness and safety of short-term (< three months) and long-term (> three months) dynamic exercise therapy programs (aerobic capacity and/or muscle strength training), either land or water-based, for people with RA. To do this we updated a previous Cochrane review (van den Ende 1998) and made categories for the different forms of dynamic exercise programs. SEARCH STRATEGY: A literature search (to December 2008) within various databases was performed in order to identify randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs that included an exercise program fulfilling the following criteria were selected: a) frequency at least twice weekly for > 20 minutes; b) duration > 6 weeks; c) aerobic exercise intensity > 55% of the maximum heart rate and/or muscle strengthening exercises starting at 30% to 50% of one repetition maximum; and d) performed under supervision. Moreover, the RCT included one or more of the following outcome measures: functional ability, aerobic capacity, muscle strength, pain, disease activity or radiological damage. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible studies, rated the methodological quality, and extracted data. A qualitative analysis (best-evidence synthesis) was performed and, where appropriate, a quantitative data analysis (pooled effect sizes). MAIN RESULTS: In total, eight studies were included in this updated review (two additional studies). Four of the eight studies fulfilled at least 8/10 methodological criteria. In this updated review four different dynamic exercise programs were found: (1) short-term, land-based aerobic capacity training, which results show moderate evidence for a positive effect on aerobic capacity (pooled effect size 0.99 (95% CI 0.29 to 1.68). (2) short-term, land-based aerobic capacity and muscle strength training, which results show moderate evidence for a positive effect on aerobic capacity and muscle strength (pooled effect size 0.47 (95% CI 0.01 to 0.93). (3) short-term, water-based aerobic capacity training, which results show limited evidence for a positive effect on functional ability and aerobic capacity. (4) long-term, land-based aerobic capacity and muscle strength training, which results show moderate evidence for a positive effect on aerobic capacity and muscle strength. With respect to safety, no deleterious effects were found in any of the included studies. AUTHORS' CONCLUSIONS: Based on the evidence, aerobic capacity training combined with muscle strength training is recommended as routine practice in patients with RA.
19010978 Mast cell chymase contributes to the antibody response and the severity of autoimmune arth 2009 Mar Mast cells are implicated in rheumatoid arthritis, but the mechanism by which they contribute to disease progression is not clarified. Here we investigated whether mouse mast cell protease-4 (mMCP-4), a chymase present in the mast cell secretory granule, contributes to experimental arthritis. Two models of arthritis were investigated in mMCP-4(+/+) and mMCP-4(-/-) DBA/1 mice: collagen-induced arthritis (CIA) was induced by immunization with collagen II (CII) in Freund's complete adjuvant, and a passive model of arthritis was induced by administration of anti-CII antibodies. The clinical scores were significantly reduced in the mMCP-4(-/-) animals as compared to mMCP-4(+/+) controls in both arthritis models. In CIA, the number of affected paws was lower in the CII-immunized mMCP-4(-/-) mice, with less cartilage destruction, pannus formation, and mononuclear cell and mast cell influx in the mMCP-4(-/-) joints. Interestingly, the lower clinical scores in the CII-immunized mMCP-4(-/-) mice coincided with lower serum levels of immunoglobulin G anti-CII antibodies. Our findings identify a pathogenic role of mMCP-4 in autoimmune arthritis.