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ID PMID Title PublicationDate abstract
24332807 The comparison of effects of biologic agents on rheumatoid arthritis damage progression is 2014 Jun OBJECTIVES: To indirectly compare the 12-month effects of available biologic agents in slowing RA radiographic progression. METHODS: A systematic review of literature of randomised, double-blind, controlled trials (RCTs) evaluating RA radiographic progression as end point was conducted using a PubMed searching of MEDLINE from January 1995 to May 2012. For each trial, the mean change from baseline of the standardised annual radiographic progression score (weighted for estimated annual progression rate) was estimated, and the effect size was calculated as the difference between biologic and non-biologic-treated groups. In order to optimise data homogeneity and improve RCTs comparison, a mixed-effect model was applied including previous responsiveness to methotrexate (MTX-experienced or MTX-naïve populations) and period of study enrollment as moderators. RESULTS: The PubMed search resulted in 183 references, and 14 were eligible for the meta-analysis. The analysis of study distribution in forest plots showed a high correlation between the study period of enrollment and the impact of biological therapy in both MTX-naïve and MTX-experienced subgroups. In particular, effect size was the highest for older trials and progressively decreased in the most recent ones, suggesting a highest propensity to radiographic progression in populations enrolled in older trials. Some statistically significant differences among RCTs were found in both subgroups but were significantly biased by the different propensity to radiographic progression due to period of enrollment. CONCLUSIONS: Our meta-analysis demonstrated that period of enrollment deeply influence study population propensity to radiographic progression in each trial. This finding does not allow the indirect comparison of various biologic agents, despite our mixed-model significantly reducing heterogeneity among RCTs.
24252041 Gastroesophageal reflux disease in patients with rheumatoid arthritis. 2014 Mar OBJECTIVE: Patients with rheumatoid arthritis (RA) are frequently complicated with gastric mucosal injury; however, there are few reports investigating gastroesophageal reflux disease (GERD) among patients with RA. We investigated the frequency of GERD and the correlation between GERD and the clinical characteristics of RA including patient's global assessment (PGA). METHODS: Patients with RA were investigated for GERD using self-administered frequency scale for the symptoms of GERD (FSSG). The correlation between GERD and the clinical characteristics of RA was analyzed statistically. RESULTS: Two hundred and eleven patients in Japan were investigated. The prevalence of GERD among patients with RA (24.6%) was significantly higher than that in the Japanese population (11.5%) (p < 0.001). FSSG was positively correlated with modified health assessment questionnaire (mHAQ), PGA, evaluator's global assessment (EGA) (p < 0.001), disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) (p < 0.05), DAS28-C-reactive protein (CRP), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) (p < 0.001). The patients with GERD showed significantly higher scores in mHAQ, PGA, EGA, tenderness joint count, DAS28-ESR, DAS28-CRP, SDAI and CDAI (p < 0.001). Furthermore, the patients with GERD showed lower remission rates based on DAS28-ESR (p < 0.05), DAS28-CRP, SDAI and CDAI (p < 0.001). CONCLUSION: GERD complicated with RA increases PGA and the indices of disease activity. GERD symptoms analyzed using FSSG may be desirable to avoid the overestimation as part of the total management of patients with RA.
23398787 Thiopurine S-methytransferase gene polymorphism in rheumatoid arthritis. 2013 Feb BACKGROUND AND AIMS: Thiopurine S-methyltransferase (TPMT) is responsible for inactivation of thiopurine drugs which are commonly used in leukemia, organ transplantation and autoimmune diseases. The gene encoding TPMT is polymorphic, and both phenotyping and genotyping studies have shown ethnic variations in gene sequence and enzyme activity worldwide. The aim of this study is to identify the most common genetic polymorphisms of TPMT in healthy Jordanian volunteers and patients with rheumatoid arthritis (RA). METHODS: A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to identify the frequency of TPMT (*2, *3A, *3B, and *3C) polymorphisms in 250 healthy Jordanian volunteers and 110 RA patients. RESULTS: Only four healthy subjects (1.6%) and one RA patient (0.9%) with variant alleles were identified in this study. Two healthy subjects had the TPMT*3A allele and the other two had the TPMT*3B allele, whereas the one RA patient had the TPMT*3A allele. No homozygous polymorphisms were detected and all genotypes detected were heterozygous (*1/*3A) (*1/*3B). None of the subjects had TPMT*2 or TPMT*3C variant alleles. CONCLUSIONS: Mutant alleles identified in this study have a low frequency. TPMT (*3A and *3B) were the only detected heterozygous alleles. No homozygous variant allele was detected. Further studies are necessary to identify other variant alleles that might uniquely occur in Jordanians.
24797672 Making the invisible visible: bioelectrical impedance analysis demonstrates unfavourable b 2014 OBJECTIVES: To examine differences between the assessment of body composition by body mass index (BMI) and bioelectrical impedance analysis (BIA) in patients with rheumatoid arthritis (RA). METHOD: The body composition of RA patients was assessed during their visit to the outpatient department of a Dutch academic hospital using BMI, fat-free mass index (FFMI), and fat mass index (FMI). FFMI and FMI were determined by single-frequency BIA. RESULTS: Sixty-five consecutive RA patients (83% women, mean age 58 years, median disease duration 7 years) with moderately active disease [mean Disease Activity Score using 28 joint counts (DAS28) = 3.40; mean Rheumatoid Arthritis Disease Activity Index (RADAI) score = 3.49] and moderate disability [mean Health Assessment Questionnaire (HAQ) score = 0.87] were included. Based on BMI, 2% of our study population were underweight, 45% had a healthy body composition, and 54% were overweight or obese. Based on BIA, 18% of the patients showed a low FFMI and 74% had a high or very high FMI. Low FFMI was found in 44% of the women with a normal BMI, and high FMI was found in 40% of the women and 75% of the men with a normal BMI. CONCLUSIONS: A high frequency of unfavourable body composition, predominantly reduced FFMI and elevated FMI, was found in a cohort of RA patients with moderately active disease, turning BMI into an unreliable method for assessment of body composition in RA. BIA, however, might be the preferred method to assess FFMI and FMI in RA patients in clinical practice, as it is easy to use and relatively inexpensive.
25407644 Predictive value of anti-citrullinated peptide antibodies: a real life experience. 2014 Dec Rheumatoid Arthritis (RA) is an autoimmune destructive joint disease, characterized by the presence of rheumatoid factor and anti-citrullinated peptide antibodies. Anti-citrullinated peptide antibodies were recently defined as RA criterion with sensitivity and specificity of 50-80 and 75-95 %, respectively. However, in the general population, the predictive value of anti-citrullinated peptide antibodies is yet to be determined. Herein, we aim to determine the predictive value of anti-citrullinated peptide antibodies in real life as well as clinical and serological factors related to this value. Retrospective cross-sectional study of consecutive samples evaluated for anti-citrullinated peptide antibodies in a referral autoimmune laboratory. Demographic and clinical parameters at the time the sample was drawn were collected. During November 2011 through December 2013, a total of 215 anti-citrullinated peptide antibody tests were performed in our laboratory. Data were available for 140 samples of which only 28 samples were positive for anti-citrullinated peptide antibodies. Of the 140 patients tested, 18 were diagnosed with RA, of which 12 were positive and 6 were negative for anti-citrullinated peptide antibody test. Thus, in this cohort, anti-citrullinated peptide antibodies were positive in 20 % of samples with a positive predictive value (PPV) of 43 % and a negative predictive value of 95 %. In real life, only 20 % of anti-citrullinated peptide antibody tests referred to a tertiary center where found to be positive. The negative predictive value of this test is very high and may support the common use of anti-citrullinated peptide antibody test as an exclusion criterion in the process of evaluating a patient with rheumatic disease.
25366699 Correlations between patient satisfaction and ability to perform daily activities after to 2015 Jan BACKGROUND: Patient satisfaction has become an important parameter for assessing overall outcomes after total knee arthroplasty (TKA). The level of difficulty in performing activities of daily life that affects overall patient satisfaction is unknown. We therefore evaluated the influence of difficulty in performing activities of daily life on patient satisfaction and expectations. METHODS: The 2011 Knee Society Knee Scoring System Questionnaire was mailed to patients who had undergone TKA with 375 patients completing and returning it. We evaluated the relationship between the ability to perform daily activities, as assessed via the questionnaire, and patient satisfaction and expectations of the same score in each patient using linear regression analysis. We also determined which activities affected patient satisfaction and expectations using multivariate linear regression analyses. RESULTS: All patient-derived functional activities correlated significantly with the patient satisfaction score. In particular, "climbing up or down a flight of stairs" followed by "getting into or out of a car," "moving laterally (stepping to the side)" and "walking and standing" correlated strongly with patient satisfaction by linear regression analysis and were revealed to have significant contributions to patient satisfaction by multivariate linear regression analysis. Regarding expectations, all patient-derived functional activities correlated significantly with the patient expectation score, although none of the correlation coefficients was very high. "Squatting," followed by "walking and standing," contributed to the patient expectation score by multivariate linear regression analysis. CONCLUSION: Activities related to walking and standing are some of the most basic movements and basic demands for patients. In addition, "climbing up or down a flight of stairs," "getting into and out of a car" and "squatting" are very important and distressing activities that significantly correlate with patient satisfaction after TKA.
25288785 Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted del 2015 Feb Mesenchymal stem cells (MSCs) are multipotent cells with the capacity to undergo chondrogenic differentiation. Systemically administered MSCs have been shown to preferentially accumulate at sites of tissue damage and inflammation, thus MSC-based therapy holds great promise for the treatment of inflammatory diseases such as RA. Modulation of MSC homing may allow targeted delivery of systemically administered MSCs to damaged articular cartilage, where they can suppress immune-mediated cartilage destruction and contribute to cartilage repair via a combination of chondrogenic differentiation and paracrine stimulation of intrinsic residual repair. To harness the potential of MSC homing, a thorough understanding of the mechanism is key. This review discusses current knowledge of the mechanism of MSC homing to injured/inflamed tissue and its implications for targeted MSC-based therapy in arthritis.
25131223 Tartrate-resistant acid phosphatase 5b is a potential biomarker for rheumatoid arthritis: 2014 BACKGROUND: Bone damage around the joints is one of the major pathophysiological mechanisms that leads to rheumatoid arthritis (RA) chronic disability. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) is secreted by osteoclasts, its activity can be used as a clinically relevant bone resorption marker. The aim of this study was to test whether the measurement of serum levels of TRACP-5b in patients with RA would correlate with measures of disease activity and with responses to therapy. METHODS: Fifty-six patients were randomly assigned to receive recombinant human cytotoxic tlymphocyte-associated antigen-4 immunoglobulin (RhCTLA4-Ig), infliximab or methotrexate (MTX). The clinical and serologic indicators of RA activity were evaluated at baseline and at 24 weeks. Serum TRACP-5b was measured by Enzyme-linked Immunosorbent Assay (ELISA) at 0, 12 and 24 weeks. Hand X-rays were obtained at baseline. RESULTS: At baseline, the levels of TRACP-5b correlated with the severity of X-ray damage, disease duration (r = 0.332, P = 0.012), and tender joint count (r = 0.408, P = 0.002). The 24 weeks values of TRACP-5b for RhCTLA4-Ig group and infliximab group differed significantly from the baseline values in each group (P < 0.05; P < 0.05), whereas only the value for RhCTLA4-Ig group differed significantly from the 24 weeks value for the MTX group (P < 0.01). Considering the two biologics-treated groups together, the TRACP-5b levels at 24 weeks differed significantly from the baseline values only in those patients who reached an ACR70 level (P < 0.05). CONCLUSIONS: Measurement of serum TRACP-5b in RA patients reflects clinical and radiological measures of disease activity, treatment with certain biologics, and degree of response to therapy. TRACP-5b should be investigated further as a potential biomarker to predict response to therapy, including slowing of radiographic progression.
23646104 Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large 2013 BACKGROUND: BANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a risk factor in rheumatoid arthritis (RA), reports are conflicting about the contribution of BANK1 to RA susceptibility. To ascertain the real impact of BANK1 on RA genetic susceptibility, we performed a large meta-analysis including our original data and tested for an epistatic interaction between BANK1 and BLK in RA susceptibility. PATIENTS AND METHODS: We investigated data for 1,915 RA patients and 1,915 ethnically matched healthy controls genotyped for BANK1 rs10516487 and rs3733197 and BLK rs13277113. The association of each SNP and RA was tested by logistic regression. Multivariate analysis was then used with an interaction term to test for an epistatic interaction between the SNPs in the 2 genes. RESULTS: None of the SNPs tested individually was significantly associated with RA in the genotyped samples. However, we detected an epistatic interaction between BANK1 rs3733197 and BLK rs13277113 (P(interaction)  = 0.037). In individuals carrying the BLK rs13277113 GG genotype, presence of the BANK1 rs3733197 G allele increased the risk of RA (odds ratio 1.21 [95% confidence interval 1.04-1.41], P = 0.015. Combining our results with those of all other studies in a large trans-ethnic meta-analysis revealed an association of the BANK1 rs3733197 G allele and RA (1.11 [1.02-1.21], P = 0.012). CONCLUSION: This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. Our results illustrate the concept of pleiotropic epistatic interaction, suggesting that BANK1 and BLK might play a role in RA pathogenesis.
23574578 Pharmacokinetic consideration of synthetic DMARDs in rheumatoid arthritis. 2013 Aug INTRODUCTION: Current treatment strategy for rheumatoid arthritis (RA) focuses on tight disease control and remission. The present understanding of the immune-pathological process of RA, mechanism of synthetic DMARDs and the clinical experience of the drugs have raised certain concerns over their clinical use. AREAS COVERED: The review summarizes latest concepts in the pathogenesis of RA, and the mechanism of action and pharmacokinetics of commonly used synthetic DMARDs. It also covers the principle of enzyme and receptor kinetics, and limitation of current knowledge on RA disease measures. EXPERT OPINION: There is a need to rationalize the use of synthetic DMARDs to help improve RA treatment. One recommendation to assist the rationalization of this treatment is by the construction of suitable models of the disease process, thereby augmenting treatment options. Currently, the dosage and duration of this type of treatment is based on its overall effect and clinical outcome. Each DMARD will confer its effect on a specific component of the multilevel, multicellular, pathological process of RA. Furthermore, developing definitive biomarkers could help to better assess the disease at its various stages instead of using conventional RA measures for drug titration and to help in the rationalization of drug regimen. Integrating pharmacokinetic and pharmacodynamic properties into this model will also help in improving treatment outcomes.
23450527 Erythropoiesis-stimulating agents for anemia in rheumatoid arthritis. 2013 Feb 28 BACKGROUND: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder that mainly affects the small joints of the hands and feet. Erythropoiesis-stimulating agents have been used to treat anemia, one of the extra-articular manifestations of RA. Although anemia is less of a problem now because of the reduction in inflammation due to disease-modifying antirheumatic drugs (DMARDs), it could still be an issue in countries where DMARDs are not yet accessible. OBJECTIVES: We assessed the clinical benefits and harms of erythropoiesis-stimulating agents for anemia in rheumatoid arthritis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (issue 7 2012), Ovid MEDLINE and Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations (1948 to 7 August 2012), OVID EMBASE (1980 to 7 August 2012), LILACS (1982 to 7 August 2012), the Clinical Trials Search Portal of the World Health Organization, reference lists of the retrieved publications and review articles. We did not apply any language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in patients aged 16 years or over, with a diagnosis of rheumatoid arthritis affected by anemia. We considered health-related quality of life, fatigue and safety as the primary outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently performed trial selection, risk of bias assessment, and data extraction. We estimated difference in means with 95% confidence intervals (CIs) for continuous outcomes. We estimated risk ratios with 95% CIs for binary outcomes. MAIN RESULTS: We included three RCTs with a total of 133 participants. All trials compared human recombinant erythropoietin (EPO), for different durations (8, 12 and 52 weeks), versus placebo. All RCTs assessed health-related quality of life. All trials had high or unclear risk of bias for most domains, and were sponsored by the pharmaceutical industry. Two trials administered EPO by a subcutaneous route while the other used an intravenous route.We decided not to pool results from trials, due to inconsistencies in the reporting of results.Health-related quality of life: subcutaneous EPO - one trial with 70 patients at 52 weeks showed a statistically significant difference in improvement of patient global assessment (median and interquartile range 3.5 (1.0 to 6.0) compared with placebo 4.5 (2.0 to 7.5) (P = 0.027) on a VAS scale (0 to 10)). The other shorter term trials (12 weeks with subcutaneous EPO and eight weeks with intravenous administration) did not find statistically significant differences between treatment and control groups in health-related quality of life outcomes.Change in hemoglobin: both trials of subcutaneous EPO showed a statistically significant difference in increasing hemoglobin levels; (i) at 52 weeks (one trial, 70 patients), intervention hemoglobin level (median 134, interquartile range 110 to 158 g/litre) compared with the placebo group level (median 112, interquartile range; 86 to 128 g/litre) (P = 0.0001); (ii) at 12 weeks (one trial, 24 patients) compared with placebo (difference in means 8.00, 95% CI 7.43 to 8.57). Intravenous EPO at eight weeks showed no statistically significant difference in increasing hematocrit level for EPO versus placebo (difference in means 4.69, 95% CI -0.17 to 9.55; P = 0.06).Information on withdrawals due to adverse events was not reported in two trials, and one trial found no serious adverse events leading to withdrawals. None of the trials reported withdrawals due to high blood pressure, or to lack of efficacy or to fatigue. AUTHORS' CONCLUSIONS: We found conflicting evidence for erythropoiesis-stimulating agents to increase quality of life and hemoglobin level by treating anemia in patients with rheumatoid arthritis. However, this conclusion is based on randomized controlled trials with a high risk of bias, and relies on trials assessing human recombinant erythropoietin (EPO). The safety profile of EPO is unclear. Future trials assessing erythropoiesis-stimulating agents for anemia in rheumatoid arthritis should be conducted by independent researchers and reported according to the CONSORT statements. Trials should be based on Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) and The Patient-Centered Outcomes Research Institute (PCORI) approaches for combining both clinician and patient perspectives.
23349128 Chronological reading of radiographs in rheumatoid arthritis increases efficiency and does 2014 Feb OBJECTIVES: To evaluate the difference between chronological and random sequence reading in a series of radiographs with 11 years' follow-up. In addition, the influence of the starting point and length of series was evaluated. METHODS: Two experienced readers independently and repeatedly scored digitised radiographs of 62 patients at time points 0, 2, 5, 8 and 11 years of follow-up from the COBRA follow-up database according to the Sharp/van der Heijde method. A linear mixed model was fitted to the data. RESULTS: Over 11 years the mean scores increased by 3.8 points per year. Compared to random reading, chronological reading resulted in a slightly increased progression rate of 0.4 points per year (p=0.008) and a lower standard error of the mean total progression rate of 0.30 (compared to 0.35 for random reading). Over 11 years, this results in a small difference in progression estimates of about five points, but a highly relevant difference of over 25% of patients needed in a study to find a difference in radiological outcome between two groups. Reading of short series, or series including a baseline radiograph, results in a significantly higher yearly progression rate compared to reading of long series, or series not including a baseline measurement. CONCLUSIONS: Chronological reading of radiographs is preferred above random reading, due to decreased variability around the estimation of the progression rate; this increased efficiency translates into smaller sample sizes, or increased power to detect small differences. For studies with long-term follow-up, the same two readers should read all radiographs, including baseline.
23665746 Does rheumatoid arthritis have an effect on audiovestibular tests? 2014 Jun The study aimed to determine the characteristics of hearing loss, vestibular responses and the incidence of vestibular disturbances in RA patients. This prospective study was performed at the Otolaryngology Department of Bozok University School of Medicine between May and November 2012. Eighty-one RA patients (69 women and 12 men) with a mean age of 40.8 ± 13.4 years (23-67 years) and 81 healthy controls (67 women and 14 men) with a mean age of 41.3 ± 13.8 years (24-66 years). Each subject was tested with low and high-frequency audiometry by a single experienced investigator under standard audiometric testing conditions. For each set of tests, mean values of air and bone conduction at each frequency and tympanometric values were calculated for the study groups. Videonystagmography (VNG) including smooth pursuit, saccade, positional, and caloric tests were also performed. The mean air conduction threshold values at high frequencies (4,000, 6,000, and 8,000 Hz) in RA group were lower than control groups. The difference between mean air conduction threshold values of the control groups against RA group at high frequencies were statistically significant (p < 0.05). There was no statistically significance between the two groups in tympanometric values (p < 0.05). VNG testing revealed central abnormalities in twenty patients (24.69%), peripheral abnormalities in five patients (6.17%), and mixed abnormalities in six patients (7.4%). There was no association between VNG abnormalities in patients with RA and age, sex, duration of disease, accompanying vertigo complaint, the laboratory findings and hearing levels (p < 0.05). Our findings suggest an association of RA and audiovestibular system dysfunction regardless clinical and demographic situation of patients. We assume the hearing and vestibular disturbances in RA are more prevalent than previously recognized. Also hearing losses in high frequencies in RA patients may be considered as an indicator of cochlear involvement in this disease.
23192908 Positive synovial vascularity in patients with low disease activity indicates smouldering 2013 Mar OBJECTIVE: To investigate the relationship between synovial vascularity and joint damage progression in each finger joint of patients with RA under low disease activity during treatment with biologic agents. METHODS: We studied 310 MCP and 310 PIP joints of 31 patients with active RA who were administered adalimumab (ADA) or tocilizumab (TCZ). Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at weeks 8, 20 and 40. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and at week 50. RESULTS: Composite scores of the DAS with 28 joints and the Simplified Disease Activity Index (SDAI) were significantly decreased from baseline to week 8, being sustained at a low level by biologic agents during the observational period. MCP and PIP joints with positive synovial vascularity after week 8 showed more subsequent joint damage progression than joints without synovial vascularity throughout the follow-up. The changes in radiographic progression in these joints were independent of the sum of synovial vascularity from baseline to week 40 or the occasional occurrence of positive synovial vascularity. CONCLUSION: Smouldering inflammation reflected by positive synovial vascularity under low disease activity was linked to joint damage. The damage progressed irrespective of the severity of positive synovial vascularity. Even with a favourable overall therapeutic response, monitoring of synovial vascularity has the potential to provide useful joint information to tailor treatment strategies. Trial registration. University Hospital Medical Information Network Clinical Trials Registry; http://www.umin.ac.jp/ctr/; UMIN000004476.
24604047 Validity of SW982 synovial cell line for studying the drugs against rheumatoid arthritis i 2014 Jan BACKGROUND & OBJECTIVES: To study effects of drugs against rheumatoid arthritis (RA) synoviocytes or fibroblast like synoviocytes (FLS) are used. To overcome the drawbacks of using FLS, this study was conducted to show the validity of SW982 synovial cell line in RA study. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V propidium iodide (PI) staining, mitochondrial membrane potential assay, Triton X-114 Phase partitioning, and immunolot for apoptosis signaling in SW982 human synovial cell line were performed. RESULTS: Fluvastatin induced apoptosis in a dose- and time-dependent manner in TNFα -stimulated SW982 human synovial cells. A geranylgeranylpyrophosphate (GGPP) inhibitor, but not a farnesylpyrophosphate (FPP) inhibitor, induced apoptosis, and fluvastatin-induced apoptosis was associated with the translocation of isoprenylated RhoA and Rac1 proteins from the cell membrane to the cytosol. Fluvastatin-induced downstream apoptotic signals were associated with inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Accordingly, 89 kDa apoptotic cleavage fragment of poly (ADP-ribose) polymerase (PARP) was detected. INTERPRETATION & CONCLUSIONS: Collectively, our data indicate that fluvastatin induces apoptotic cell death in TNFα-stimulated SW982 human synovial cells through the inactivation of the geranylgerenylated membrane fraction of RhoA and Rac1 proteins and the subsequent inhibition of the PI3K/Akt signaling pathway. This finding shows the validity of SW982 cell line for RA study.
23397147 Inflammatory immune cell responses and Toll-like receptor expression in synovial tissues i 2013 Jun Biologic antirheumatic drugs (BIO) have been reported to be potent therapeutic agents in the prevention of inflammatory joint destruction in rheumatoid arthritis (RA). The aim of this study was to investigate the immune-inflammatory cells, including Toll-like receptor (TLR)-equipped cells, in synovial tissue samples from RA patients on BIO compared to patients, who are only on conventional disease-modifying antirheumatic drug (DMARD). We analyzed immune-inflammatory cells in RA synovitis in patients of BIO group (n = 20) or DMARD group (n = 20). The grading scores of synovitis was 1.7 and 1.8 in each BIO and DMARD group and correlated best with the CD3(+) T (r = 0.71/0.70, p < 0.05) and CD20(+) B (r = 0.80/0.84, p < 0.05) cells in the both groups, but less well with the CD68(+) macrophages and S-100(+) dendritic cells (DCs). Interestingly, both T (116 vs. 242, p < 0.05) and B (80 vs. 142, p < 0.05) cell counts were lower in the BIO than in the DMARD group, whereas macrophage and DC counts did not differ. In contrast, the C-reactive protein (CRP) and disease activity score DAS28-CRP did not show clear-cut correlations with the inflammatory grade of the synovitis (r range, 0-0.35). Similar numbers of cells immunoreactive for TLR-1 to TLR-6 and TLR-9 were found in synovitis in both groups. Patients clinically responding to biologics might still have the potential of moderate/severe local joint inflammation, composed in particular of and possibly driven by the autoinflammatory TLR(+) cells.
23698472 Do rehabilitation tools cover the perspective of patients with rheumatoid arthritis? A foc 2014 Apr BACKGROUND: Despite the advocated use of rehabilitation tools in clinical rehabilitation of with rheumatoid arthritis (RA) patients, little is known about the representation of the patient perspective in these tools. AIM: Aim of the study was to explore the experiences of RA patients with rehabilitation and the coverage by rehabilitation tools. DESIGN AND POPULATION: Qualitative focus group study with RA patients about experiences with rehabilitation. SETTING: Rheumatology rehabilitation clinic of a Dutch university hospital. METHODS: Focus groups were tape recorded and transcribed verbatim. From the meaningful units, concepts were extracted and linked to the International Classification of Functioning, Disability and Health (ICF). Rehabilitation tools validated for RA were identified using a structured literature search. Using the ICF as common framework, we determined for each concept identified in the focus groups the coverage by each rehabilitation tool. RESULTS: Nineteen patients participated in 4 focus groups. Fifty-one concepts were identified in 368 meaningful units derived from the transcribed data. From the literature the ICF Core Sets for RA, Canadian Occupational Performance Measure, Rehabilitation Activities Profile and WHO Disability Assessment Schedule II were elected. The concepts from the focus groups were best covered by the ICF Core Sets (44 out of 51; 86%), followed by the WHODAS II (39%), RAP (35%) and COPM (16%). CONCLUSION: With the exception of the ICF Core Sets for RA, current rehabilitation tools poorly cover the RA patients' perception on rehabilitation. CLINICAL REHABILITATION IMPACT: The ICF Core Sets can serve as a checklist to guide multidisciplinary assessment, goal-setting and evaluation in RA rehabilitation.
23629430 [Comparison of nine second- and third-generation anti-cyclic citrullinated peptide antibod 2013 The aim of this study was to compare the diagnostic and analytical performances of nine anti-cyclic citrullinated peptide (CCP) antibody assays. Anti-CCP antibody titers were measured in sera from 89 patients with rheumatoid arthritis (RA), 121 with rheumatic diseases other than RA (non-RA), 47 with osteoarthritis (OA), 142 with chronic inflammatory diseases (CID) and 168 healthy subjects. Reproducibility, sensitivity, specificity, correlation and concordance rate of the nine assays were compared. Coefficients of variations of within-run and between-run reproducibility at two different concentrations for each assay ranged from 0.7 to 8.5% and from 0.6 to 8.3%, respectively. With our proposed optimal cut-off value for the third-generation assay, concordance rates were 96.8~99.6%. The range of sensitivity was 75.3~78.7% and the ranges of specificity for non-RA, OA, CID, and healthy subjects were 93.4~97.5%, 97.9%, 96.5~98.6% and 98.8~100%, respectively. However, several discrepant samples were detected and their titer levels were about 3 times higher than the normal upper limit in the 2010 RA classification criteria. Good positive correlations were observed for parts of the second-generation assay. Our study showed that each of the nine assays has good reproducibility and high diagnostic accuracy, and is thus equally useful for the diagnosis of RA.
24990235 Surface expression of CD39 identifies an enriched Treg-cell subset in the rheumatic joint, 2014 Oct Treg cells are important for the maintenance of self-tolerance and are implicated in autoimmunity. Despite enrichment of Treg cells in joints of rheumatoid arthritis (RA) patients, local inflammation persists. As expression of the ATP-hydrolyzing enzymes CD39 and CD73 and the resulting anti-inflammatory adenosine production have been implicated as an important mechanism of suppression, we characterized FOXP3(+) Treg cells in blood and synovial fluid samples of RA patients in the context of CD39 and CD73 expression. Synovial FOXP3(+) Treg cells displayed high expression levels of rate-limiting CD39, whereas CD73 was diminished. FOXP3(+) CD39(+) Treg cells were also abundant in synovial tissue. Furthermore, FOXP3(+) CD39(+) Treg cells did not secrete the proinflammatory cytokines IFN-γ and TNF after in vitro stimulation in contrast to FOXP3(+) CD39(-) T cells. FOXP3(+) CD39(+) Treg cells could be isolated by CD39 and CD25 coexpression, displayed a demethylated Treg-specific demethylated region and coculture assays confirmed that CD25(+) CD39(+) T cells have suppressive capacity, while their CD39(-) counterparts do not. Overall, our data show that FOXP3(+) CD39(+) Treg cells are enriched at the site of inflammation, do not produce proinflammatory cytokines, and are good suppressors of many effector T-cell functions including production of IFN-γ, TNF, and IL-17F but do not limit IL-17A secretion.
24941526 [Epidemiology of physical disabilities in France]. 2014 May Neurological pathologies and conditions affecting the musculoskeletal system have significant effects on motor skills. Bone and joint disabilities are the most common but the most severe disabilities are linked to neurological conditions, particularly as they are often associated with cognitive deficits.