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ID PMID Title PublicationDate abstract
21540202 Self-management of fatigue in rheumatoid arthritis: a randomised controlled trial of group 2011 Jun OBJECTIVES: To investigate the effect of group cognitive behavioural therapy (CBT) for fatigue self-management, compared with groups receiving fatigue information alone, on fatigue impact among people with rheumatoid arthritis (RA). METHODS: Two-arm, parallel randomised controlled trial in adults with RA, fatigue ≥ 6/10 (Visual Analogue Scale (VAS) 0-10, high bad) and no recent change in RA medication. Group CBT for fatigue self-management comprised six (weekly) 2 h sessions, and consolidation session (week 14). Control participants received fatigue self-management information in a 1 h didactic group session. Primary outcome at 18 weeks was the impact of fatigue measured using two methods (Multi-dimensional Assessment of Fatigue (MAF) 0-50; VAS 0-10), analysed using intention-to-treat analysis of covariance with multivariable regression models. RESULTS: Of 168 participants randomised, 41 withdrew before entry and 127 participated. There were no major baseline differences between the 65 CBT and 62 control participants. At 18 weeks CBT participants reported better scores than control participants for fatigue impact: MAF 28.99 versus 23.99 (adjusted difference -5.48, 95% CI -9.50 to -1.46, p=0.008); VAS 5.99 versus 4.26 (adjusted difference -1.95, 95% CI -2.99 to -0.90, p<0.001). Standardised effect sizes for fatigue impact were MAF 0.59 (95% CI 0.15 to 1.03) and VAS 0.77 (95% CI 0.33 to 1.21), both in favour of CBT. Secondary outcomes of perceived fatigue severity, coping, disability, depression, helplessness, self-efficacy and sleep were also better in CBT participants. CONCLUSIONS: Group CBT for fatigue self-management in RA improves fatigue impact, coping and perceived severity, and well-being. TRIAL REGISTRATION: ISRCTN 32195100.
22956168 [Secondary vasculitides and vasculitis mimics]. 2012 Nov Secondary vasculitis is a form of vasculitis for which an underlying disease is known. Diseases associated with secondary vasculitis include infections, drug hypersensitivity, malignancy, rheumatoid arthritis, collagen vascular disease and sarcoidosis. Moreover, there are numerous conditions that can mimic vasculitis clinically, in laboratory testing, radiographically and in histopathology. It is evident that distinguishing primary vasculitis from secondary vasculitis and also vascular inflammation from non-vasculitic disorders (vasculitis mimics) has significant therapeutic implications.
21635793 Ultrasound in rheumatoid arthritis: volar versus dorsal synovitis evaluation and scoring. 2011 Jun 3 BACKGROUND: Assessment of synovitis in rheumatoid arthritis (RA) is a major issue for a proper treatment administration; it has been proven that ultrasound (US) examination could be of valuable help and it is currently being investigated as a possible outcome measure for the disease. It is, though, of greatest importance to accurately establish the place of US scores among the already validated outcome measures, according to Outcome Measures for Rheumatoid Arthritis in Clinical Trials (OMERACT) filter. The present study is designed to compare the results of gray-scale ultrasound (GSUS) and Power Doppler ultrasound (PDUS) additive scores, separately calculated for volar and dorsal aspects of the hand, with physical examination, patient's evaluation of disease pain and global activity on Visual Analogic Scale (VAS) and traditional scores for disease activity assessment (DAS28, CDAI, SDAI, HAQ). The final aim is to prove the advantages of volar US evaluation in RA patients. METHODS: 42 RA patients have been clinically evaluated for pain and swelling of their hand joints, completed VAS and HAQ questionnaires and underwent both volar and dorsal sonography of the hands during the same day. The US examiner was blinded to clinical assessments and lab results. For each patient 20 joints were assessed by sonography (radiocarpal, intercarpal, metacarpophalangeal (MCP) 2-5, proximal interphalangeal (PIP) 2-5). Carpal joints were only evaluated from dorsal view, while MCPs and PIPs were evaluated both from dorsal and volar aspect resulting a total of 36 distinct evaluations for each patient. GSUS synovial hypertrophy was assessed both by quantitative measurement and semiquantitative scale (0-3 grades); Doppler signal (PDUS) was recorded on a semiquantitative scale (0-3 grades). The semiquantitative grades for both GSUS and PDUS evaluation of each joint were added and the sum was defined as the Echographic Score (ES) of each patient. Separately, we added the semiquantitative grades for volar and dorsal side, resulting in Volar ES (VES) and Dorsal ES (DES) of each patient. RESULTS: We found ESs correlated with other activity scores: DAS28, CDAI, SDAI, HAQ. Correlations with clinical indices as CDAI and SDAI were stronger for VES than for DES. US discovered more synovitis than clinical examination. CONCLUSION: VES is a suitable reflection of RA activity and volar US examination should accompany the dorsal one both in clinical practice and in clinical trials.
22507344 Hepatitis C virus-related arthritis and rheumatoid arthritis: could they be different aspe 2012 Jan The role played by HCV in the genesis of many autoimmune disorders has been reported in several studies. In particular, the onset of arthritis has been described in about 2-3 percent of HCV infection cases. At present, this HCV-related arthritis is classified as a reactive arthritis, but a real distinction of this form from classical rheumatoid arthritis is often difficult. In this presentation, the Authors distinguish two arthritic forms observed in HCV-related arthritis patients: one, characterized by asymmetrical oligoarticular-involvement, and another, with poly-articular symmetrical involvement. The Authors suggest that the latter can be considered as a form of rheumatoid arthritis, because of the similarity of the main clinical aspects and laboratory findings (rheumatoid factor, anti-cyclic citrullinated peptide antibodies) to those of classical rheumatoid arthritis, which make the two forms indistinguishable. Therefore, HCV could be considered the etiologic agent of a limited number of cases of rheumatoid arthritis.
23104761 Smoking and overweight determine the likelihood of developing rheumatoid arthritis. 2013 Oct OBJECTIVES: Rheumatoid arthritis (RA) is a prototypic chronic inflammatory disease with a debilitating course if untreated. A genetic predisposition for RA is known, and its occurrence is associated with the presence of autoantibodies in the serum and with environmental factors. It is unknown if smoking and overweight are contributory factors for developing RA in individuals with RA-specific autoantibodies in the serum. METHODS: Fifty-five individuals at risk for developing RA, based on the presence of RA-specific autoantibodies in the serum, who never had any evidence of arthritis upon physical examination, were followed over time. Smoking was assessed as being never or ever smoker and body mass index as <25 (normal) or ≥25 kg/m² (overweight). Clinical endpoint was the occurrence of arthritis. Proportional hazard regression analysis was performed to investigate the potential of (combinations of) variables in predicting the onset of arthritis over time. RESULTS: After a median follow up time of 13 (IQR 6-27) months, 15 individuals (27%) developed arthritis. Smoking was associated with the development of arthritis (HR (95% CI): 9.6 (1.3 to 73.0); p=0.029). Overweight was, independently of smoking, associated with arthritis (HR (95% CI): 5.6 (1.3 to 25.0); p=0.023). The overall arthritis risk of 28% after a median of 27 months follow up increased to 60% in individuals with a smoking history combined with overweight. CONCLUSIONS: This is the first prospective study showing that smoking and overweight increase the risk of development of arthritis in a cohort of autoantibody-positive individuals at risk for developing RA. These results show the importance of life style factors in development of RA and should be critically evaluated in future clinical research aimed at disease prevention.
22353850 Plasma pyridoxal 5'-phosphate is not associated with inflammatory and immune responses aft 2012 BACKGROUND/AIMS: Plasma pyridoxal 5'-phosphate (PLP) has been shown to be associated with inflammatory and immune responses.Rheumatoid arthritis (RA) is an autoimmune and chronic systemic inflammatory disease and patients with RA have lower plasma PLP levels. We studied the relationship between plasma PLP and inflammatory or immune responses in patients with RA. METHODS: This study was designed as an observational cross-sectional study. Forty-three patients with RA were allocated to the adequate (PLP ≥20 nmol/l) (n = 30) or deficient vitamin B(6) (PLP <20 nmol/l) (n = 13) group according to their fasting plasma PLP concentration on the day blood was taken. Plasma PLP, inflammatory parameters [i.e. high-sensitivity CRP (hs-CRP), erythrocyte sedimentation rate, interleukin-6, tumor necrosis factor-α] and immune parameters (i.e. white blood cells, total lymphocytes, neutrophils, T lymphocytes, B lymphocytes, T helper cells and T suppressor cells) were measured. RESULTS: Patients with deficient plasma PLP concentration were mostly considered to have a systemic inflammatory status (hs-CRP >3 mg/l) and apparently had significantly higher mean hs-CRP levels and immune parameters than patients with adequate plasma PLP concentration. There was no significant association between plasma PLP levels and inflammatory parameters. The significantly inverse correlation of plasma PLP with the numbers of white blood cells, neutrophils, total lymphocytes, T lymphocytes and T helper cells remained after adjusting for serum hemoglobin concentration, but the significant correlation disappeared after serum albumin concentration was also considered. CONCLUSIONS: RA patients with deficient plasma PLP concentration had more severe inflammatory and immune responses than patients with adequate plasma PLP concentration. However, there was a lack of association of low plasma PLP concentration with inflammatory and immune parameters after serum albumin concentration was considered in patients with RA.
22532634 A CD4 T cell gene signature for early rheumatoid arthritis implicates interleukin 6-mediat 2012 Aug OBJECTIVE: We sought clinically relevant predictive biomarkers present in CD4 T-cells, or in serum, that identified those patients with undifferentiated arthritis (UA) who subsequently develop rheumatoid arthritis (RA). METHODS: Total RNA was isolated from highly purified peripheral blood CD4 T cells of 173 early arthritis clinic patients. Paired serum samples were also stored. Microarray analysis of RNA samples was performed and differential transcript expression among 111 'training cohort' patients confirmed using real-time quantitative PCR. Machine learning approaches tested the utility of a classification model among an independent validation cohort presenting with UA (62 patients). Cytokine measurements were performed using a highly sensitive electrochemiluminescence detection system. RESULTS: A 12-gene transcriptional 'signature' identified RA patients in the training cohort and predicted the subsequent development of RA among UA patients in the validation cohort (sensitivity 68%, specificity 70%). STAT3-inducible genes were over-represented in the signature, particularly in anti-citrullinated peptide antibody-negative disease, providing a risk metric of similar predictive value to the Leiden score in seronegative UA (sensitivity 85%, specificity 75%). Baseline levels of serum interleukin 6 (IL-6) (which signals via STAT3) were highest in anti-citrullinated peptide antibodies-negative RA and distinguished this subgroup from non-RA inflammatory synovitis (corrected p<0.05).Paired serum IL-6 measurements correlated strongly with STAT3-inducible gene expression. CONCLUSION: The authors have identified IL-6-mediated STAT-3 signalling in CD4 T cells during the earliest clinical phase of RA, which is most prominent in seronegative disease. While highlighting potential biomarker(s) for early RA, the role of this pathway in disease pathogenesis awaits clarification.
23277203 New advances of DNA methylation and histone modifications in rheumatoid arthritis, with sp 2013 Apr Epigenetics is a steadily growing research area in many human diseases, especially in autoimmune diseases such as rheumatoid arthritis (RA). RA is an autoimmune disease with unclear etiology characterized by chronic inflammation and joint destruction and fibroblast-like synoviocytes (FLS) display a crucial role in the pathogenesis of RA. Even though the etiology is not yet fully understood, RA is generally considered to be caused by a combination of epigenetic modification, deregulated immunomodulation, and environmental factors. Epigenetic modifications, including DNA methylation and post-translational histone modifications, such as histone methylation and histone (de)acetylation are identified as regulatory mechanisms in controlling aggressive FLS activation in patients and animal models. In the last 3years, the field of epigenetics in RA has impressively increased. Methyl-CpG-binding protein 2 (MeCP2) is first identified as a transcriptional repressor that inhibits gene expression through the interpretation of two epigenetic markers, DNA methylation and histone modification. The cooperative action among MeCP2, DNA methylation and histone modifications indicates that MeCP2 should participate in the pathogenesis of RA through silence of certain gene transcription. In this review, we consider the role of DNA methylation and histone modifications in the development of RA, with a special focus on increased MeCP2 expression in RA animal models.
21351303 The reliability of diagnostic coding and laboratory data to identify tuberculosis and nont 2011 Mar PURPOSE: Anti-tumor necrosis factor-alpha (anti-TNF) therapies are associated with severe mycobacterial infections in rheumatoid arthritis patients. We developed and validated electronic record search algorithms for these serious infections. METHODS: The study used electronic clinical, microbiologic, and pharmacy records from Kaiser Permanente Northern California (KPNC) and the Portland Veterans Affairs Medical Center (PVAMC). We identified suspect tuberculosis and nontuberculous mycobacteria (NTM) cases using inpatient and outpatient diagnostic codes, culture results, and anti-tuberculous medication dispensing. We manually reviewed records to validate our case-finding algorithms. RESULTS: We identified 64 tuberculosis and 367 NTM potential cases, respectively. For tuberculosis, diagnostic code positive predictive value (PPV) was 54% at KPNC and 9% at PVAMC. Adding medication dispensings improved these to 87% and 46%, respectively. Positive tuberculosis cultures had a PPV of 100% with sensitivities of 79% (KPNC) and 55% (PVAMC). For NTM, the PPV of diagnostic codes was 91% (KPNC) and 76% (PVAMC). At KPNC, ≥ 1 positive NTM culture was sensitive (100%) and specific (PPV, 74%) if non-pathogenic species were excluded; at PVAMC, ≥1 positive NTM culture identified 76% of cases with PPV of 41%. Application of the American Thoracic Society NTM microbiology criteria yielded the highest PPV (100% KPNC, 78% PVAMC). CONCLUSIONS: The sensitivity and predictive value of electronic microbiologic data for tuberculosis and NTM infections is generally high, but varies with different facilities or models of care. Unlike NTM, tuberculosis diagnostic codes have poor PPV, and in the absence of laboratory data, should be combined with anti-tuberculous therapy dispensings for pharmacoepidemiologic research.
22656185 Upregulation of tumor necrosis factor receptor-associated factor 6 correlated with synovit 2012 Jun 4 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction and disability. Focal bone erosion is due to excess bone resorption of osteoclasts. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is one of the critical mediators both in inflammatory signal pathway and differentiation and resorption activity of osteoclasts. Here we aimed to investigate TRAF6 expression in RA synovium and its correlation with histological synovitis severity and radiological joint destruction in RA. METHODS: Synovitis score was determined in needle biopsied synovium from 44 patients with active RA. Synovium from nine patients with osteoarthritis (OA) and seven with orthopedic arthropathies (Orth.A) were enrolled as "less inflamed" disease controls. Serial sections were stained immunohistochemically for TRAF6 as well as CD68 (macrophage), CD3 (T cell), CD20 (B cell), CD38 (plasmocyte), CD79a (B lineage cells from pre-B cell to plasmocyte stage), and CD34 (endothelial cell). Double immunofluorescence staining of TRAF6 and CD68 were tested. Densities of positive staining cells were determined and correlated with histological disease activity (synovitis score) and radiographic joint destruction (Sharp score). RESULTS: TRAF6 expression was found in the intimal and subintimal area of RA synovium, with intense staining found in the endochylema and nucleus of intimal synoviocytes and subintimal inflammatory cells. Double immunofluorescence staining showed TRAF6 was expressed in most of the intimal cells and obviously expressed in CD68+ cells and some other CD68- cells in subintimal area. Synovial TRAF6 was significantly over-expressed in the RA group compared with the OA and Orth.A group (2.53 ± 0.94 vs. 0.72 ± 0.44 and 0.71 ± 0.49, P < 0.0001). Synovial TRAF6 expression in RA correlated significantly with synovitis score (r = 0.412, P = 0.006), as well as the inflammatory cell infiltration (r = 0.367, P = 0.014). Significant correlation was detected between synovial TRAF6 expression and intimal CD68+ cells, as well as the cell density of subintimal CD68+ cells, CD3+ cells, CD20+ cells, CD38+ cells, and CD79a+ cells (all P < 0.05). CONCLUSIONS: Elevated synovial TRAF6 expression correlated with synovitis severity and CD68+ cell density in RA. It is, therefore, hypothesized that synovial TRAF6 is involved in the pathogenesis of synovial inflammation and osteoclast differentiation in RA.
21691912 [Total ankle arthroplasty for rheumatoid arthritis]. 2011 Jul Modern second generation total ankle arthroplasty is now a serious alternative to ankle fusion in patients with rheumatoid arthritis after careful assessment of the indications. The midterm results with 10-year survival rates between 70% and 90% and the possible revision for implant exchange or arthrodesis are the reasons for the increasing importance of ankle arthroplasty. Patients with rheumatoid arthritis in particular with generally lower physical requirements can expect a pain-free function of the operated ankle for 8-10 years. In comparison to fusion ankle arthroplasty allows a significantly faster remobilization and reserves the correction capabilities of the ankle. Arthrodesis remains a valuable therapeutic alternative for severe bony destruction and instability as well as a possible fallback for failure of arthroplasty.
21803749 Do non-steroidal anti-inflammatory drugs have a significant effect on detection and gradin 2011 Oct OBJECTIVES: To determine whether non-steroidal anti-inflammatory drugs (NSAIDs) have a significant effect on ultrasonographic (US) grey scale (GS) and power Doppler (PD) assessment of synovitis in rheumatoid arthritis (RA). METHODS: Patients with RA taking NSAIDs were randomised to either stopping (for a minimum of 5 drug half-lives) or continuing the drug. All patients had a clinical assessment and US examination of both hands and wrists before and after stopping/continuing the NSAID. Changes at follow-up were compared between groups using Mann-Whitney U tests. RESULTS: A total of 58 patients with RA were recruited. All the clinical assessment parameters (including disease activity, pain, general state of health and physician global visual analogue score and tender and swollen joints count) showed an increase in the group who stopped their NSAID treatment. The total GS and PD score showed median (first to third quartiles) increase of 9.5 (5.75 to 19.0) and 4.0 (2.0 to 6.0) per patient, respectively, in the patients who stopped their NSAID in comparison with 1.0 (-1.0 to 2.25) and 0.0 (-2.0 to 3.0), respectively, in the patients who continued their NSAID (p<0.001). There was an increase in the number of joints scoring >0 for GS and PD in the patients who stopped the NSAID. The inter- and intrareader agreement was good to excellent for the US examination. CONCLUSION: NSAID usage may mask the GS and PD signal and result in lower scoring despite continuing disease activity. Consideration should be given to the NSAID effect in designing clinical studies which use US to assess response to therapeutic.
23027887 Multiple courses of rituximab produce sustained clinical and radiographic efficacy and saf 2012 Dec OBJECTIVE: This 5-year observational posthoc analysis of the REFLEX study and its open-label extension assessed clinical efficacy, radiographic response, and safety of rituximab (RTX) in patients with rheumatoid arthritis (RA) who had an inadequate response to tumor necrosis factor (TNF) inhibitors. METHODS: Patients in REFLEX were originally randomized to placebo (PBO) + methotrexate (MTX; PBO-randomized) or RTX + MTX (RTX-randomized). PBO-randomized patients were rescued with RTX as appropriate. Patients responding to initial RTX treatment could receive further RTX courses. For clinical efficacy and safety analyses, PBO-randomized patients were re-baselined prior to first RTX treatment and the data were pooled with RTX-randomized patient data. Efficacy outcomes 24 weeks after each course were calculated relative to first RTX pretreatment baseline. Radiographic outcomes were assessed relative to randomization baseline for both PBO-randomized and RTX-randomized groups. RESULTS: A total of 480 patients received ≥ 1 RTX course. At 24 weeks, American College of Rheumatology 20/50/70 responses were 62.0%, 30.8%, and 13.0%, respectively at course 1 (n = 400) and 70.3%, 41.8%, and 22.0% at course 5 (n = 91). European League Against Rheumatism good/moderate responses were 77.2% and 84.4% at courses 1 (n = 390) and 5 (n = 90). Rates of adverse events (AE), serious AE, and infections generally remained stable. Rate of progressive joint damage (PJD; change in mean Total Sharp Score) decreased over time in both PBO-randomized (n = 79) and RTX-randomized (n = 105) groups. Mean change from baseline in PJD over 5 years was greater in PBO-randomized versus RTX-randomized patients (5.51 vs 3.21). CONCLUSION: RTX re-treatment over 5 years is associated with maintained or improved efficacy, continued inhibition of PJD, and a safety profile consistent with that previously reported. A delay in initiating RTX treatment may result in increased PJD.
21446887 Expression of human TIM-3 and its correlation with disease activity in rheumatoid arthriti 2011 OBJECTIVE: T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) is a novel transmembrane protein that is involved in the regulation of T-helper 1 (Th1)-cell-mediated immunity. This study was undertaken to investigate the expressions of TIM-3 and its ligand galectin 9 (Gal-9) with respect to disease activity in rheumatoid arthritis (RA). METHODS: Blood was collected from 39 RA patients and 31 healthy controls. Blood leucocyte TIM-3 and Gal-9 mRNA levels and RA disease activity were determined. Synovial tissue (ST) from five RA patients and five osteoarthritis (OA) patients were examined for TIM-3 mRNA expression and were also analysed for TIM-3 by immunohistology. RESULTS: TIM-3 mRNA expression was significantly higher in the ST of RA patients than in the ST of OA patients. TIM-3 was expressed in the synovial sublining area in ST of RA patients but not in OA ST. TIM-3 mRNA expression from peripheral blood mononuclear cells (PBMCs) of RA patients was negatively correlated with the 28-joint Disease Activity Score (DAS28). Gal-9 mRNA level in PBMCs of RA patients was higher than in healthy controls, and was significantly higher in patients with low disease activity compared to those with moderate to high disease activity. Gal-9 mRNA expression in PBMCs of RA patients was positively correlated with forkhead box P3 (FoxP3) mRNA expression. CONCLUSION: TIM-3 and its interaction with Gal-9 are closely associated with RA disease activity and may play an important role in the pathogenesis of RA. In addition to the negative regulatory effect of Gal-9 mediated through the TIM-3-Gal-9 pathway, Gal-9 may exert its suppressive effect on RA disease activity by modulation of regulatory T (Treg) cells.
21947347 Association of the MDR1 3435 polymorphism in patients with refractory rheumatoid arthritis 2012 Oct To evaluate whether the multidrug resistance gene 1 (MDR1) exon 26 polymorphisms are associated with the refractory rheumatoid arthritis (RRA). The study was carried out on two hundred and twenty-three patients with RA treated and one hundred and three normal controls. The RA treated were divided into two groups according the response to disease-modifying antirheumatic drugs (DMARDs). There were 108 patients in the effective group and 115 patients in the ineffective group. Genotypes of the C3435T polymorphism were determined by polymerase chain reaction followed by restriction digestion (PCR-RFLP). There were significant differences in the genotype frequency and allele frequency among three groups. Compared to responders and controls, the nonresponders carried more CC genotype (χ(2) = 5.306, P = 0.021; χ(2) = 7.810, P = 0.005) and more C allele (χ(2) = 6.601, P = 0.010; χ(2) = 12.172, P = 0.000). But, there were no statistically significant differences in genotype nor allele frequency between RA and healthy controls. The results from our study suggest that the C3435T MDR1 gene polymorphism may not be related with the RA susceptibility, but may influence the efficacy of RA therapy with DMARDs, and the 3435CC genotype may be related with RRA.
22110531 Enhanced HMGB1 expression may contribute to Th17 cells activation in rheumatoid arthritis. 2012 Rheumatoid arthritis(RA) is a common autoimmune disease associated with Th17 cells, but what about the effect of high-mobility group box chromosomal protein 1 (HMGB1) and the relationship between Th17-associated factors and HMGB1 in RA remains unknown. In the present study, we investigated the mRNA levels of HMGB1, RORγt, and IL-17 in peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis by quantitative real-time PCR (RT-qPCR), and the concentrations of HMGB1, IL-17, and IL-23 in plasma were detected by ELISA. And then, the effect of HMGB1 on Th17 cells differentiation was analyzed in vitro. Our clinical studies showed that the mRNAs of HMGB1, RORγt, and IL-17 in patients were higher than that in health control (P < 0.05), especially in active RA patients (P < 0.05). The plasma HMGB1, IL-17, and IL-23 in RA patients were also higher than that in health control (P < 0.05); there was a positive correlation between the expression levels of HMGB1 and the amount of CRP, ERS, and RF in plasma. In vitro, the IL-17-produced CD4(+)T cells were increased with 100 ng/mL rHMGB1 for 12h, which indicated that the increased HMGB1 might contribute to Th17 cells activation in RA patients.
22032620 Can anti-cyclic citrullinated peptide antibody-negative RA be subdivided into clinical sub 2011 INTRODUCTION: Studies investigating genetic risk factors for susceptibility to rheumatoid arthritis (RA) studied anti-citrullinated peptide antibody (CCP)-positive RA more frequently than anti-CCP-negative RA. One of the reasons for this is the perception that anti-CCP-negative RA may include patients that fulfilled criteria for RA but belong to a wide range of diagnoses. We aimed to evaluate the validity of this notion and explored whether clinical subphenotypes can be discerned within anti-CCP-negative RA. METHODS: The 318 patients with anti-CCP-negative RA (1987 ACR criteria), included in the Leiden Early Arthritis Clinic between 1993 and 2006, were studied for baseline characteristics and radiologic progression data during a mean follow-up of 5 years. Grouping was studied both at variable and patient levels. Principal components analysis and partial least-squares regression were applied to study for clustering of variables. A cluster analysis was performed to look for clustering of patients. RESULTS: The simultaneous presence of patient characteristics at disease presentation was observed for several groups; however, the three largest groups of patients' characteristics explained only 26.5% of the total variance. Plotting the contribution of each patient to these three groups did not reveal clustering of patients. Comparable observations were made when data on progression of joint destruction were studied in relation to baseline clinical data. A cluster analysis, evaluating whether patients resemble each other, revealed no grouping of patients. Altogether, no clinically distinguishable subphenotypes were observed. CONCLUSIONS: The current data provide evidence that, for risk-factor studies, anti-CCP-negative RA patients can be studied as one group.
20883838 Injectable hyaluronic acid-tyramine hydrogels for the treatment of rheumatoid arthritis. 2011 Feb Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by inflammation of the synovial membrane, leading in turn to articular cartilage destruction. In this work, injectable tyramine modified hyaluronic acid (HA-Tyr) hydrogels were developed for the treatment of RA. HA-Tyr conjugate was synthesized by amide bond formation between carboxyl groups of HA and amine groups of tyramine. Then, HA-Tyr hydrogels were prepared by radical crosslinking reaction using H(2)O(2) and horse-radish peroxidase. Intra-articular injection of HA-Tyr hydrogels encapsulating dexamethasone (DMT) as a model drug resulted in successful treatment of RA with reduced interlukine-6, prostaglandin E2 and four types of cytokine levels in collagen-induced arthritis animal models. Histological analysis with hematoxylin and eosin (H&E) staining also confirmed the therapeutic effect of injectable HA-Tyr hydrogels with DMT. Taken together, the injectable HA-Tyr hydrogels were thought suitable to be developed as a therapeutically effective drug carrier for the treatment of RA.
21142617 Persistence with non-selective NSAIDs and celecoxib among patients with gastroesophageal r 2011 Feb OBJECTIVE: Gastrointestinal (GI) symptoms are common in patients taking nonselective, nonsteroidal anti-inflammatory drugs (nsNSAIDs) and are often a reason for therapy discontinuation. In osteoarthritis (OA) and rheumatoid arthritis (RA) patients requiring pain control, selective COX-2 NSAID use is typically associated with less dyspepsia than is nsNSAID use. Little is known about NSAID tolerance in patients with gastroesophageal reflux disease (GERD). This study assessed nsNSAID and celecoxib prescription patterns, in particular persistence, in OA/RA patients with concomitant diagnosis of GERD. METHODS: An observational study of GERD patients with a diagnosis of OA/RA using two separate databases, the IMS Lifelink Health Plan Claims Database (PharMetrics) and Market Scan Claims Database (Medstat) was conducted. In each database, parallel and separate analyses were performed in adult patients who had their first GERD diagnosis in 2006 and who were subsequently diagnosed with OA or RA in the same year. From this subset of patients, celecoxib-naïve and nsNSAID-naïve cohorts were identified and patients were selected. Patients with pre-existing GI conditions were excluded from the study. Persistence, measured as time to discontinuation, was evaluated by Kaplan-Meier survival curves and Cox proportional hazards models. Reasons for discontinuations were not available in these databases. RESULTS: Fewer patients discontinued celecoxib as compared to nsNSAIDs during the 60 days of the first prescription and throughout the entire follow-up period. After adjusting for baseline characteristics, celecoxib patients still had significantly decreased risk of discontinuation as compared to nsNSAID patients (p < 0.0001). Replication of these observations in two separate, large patient databases increases the confidence in this study's conclusion. LIMITATIONS: Limitations include those inherent to claims data analyses and retrospective review, e.g. these data do not provide clinical information related to reasons for medication discontinuation. CONCLUSION: In patients with concomitant GERD and OA or RA who require anti-inflammatory treatment, significantly more patients treated with celecoxib were persistent with their treatment than were patients treated with nsNSAIDs.
23259629 B-cell therapies for rheumatoid arthritis. 2012 B cells were originally considered key mediators in the pathogenesis of rheumatoid arthritis (RA). The presence of these cells in many RA synovial tissues and the discovery of rheumatoid factor had put B cells originally at the center of disease pathogenesis. That enthusiasm vanished shortly thereafter only to resurface in the last 15 years with the appearance of highly specific anti-cyclic citullinated protein antibodies. Rituximab, an anti-CD20 antibody that depletes mature B cells, was approved for the treatment of RA in 2006. Since then, B cell depletion strategies have proven efficacy for advanced disease, particularly in those patients that do not respond to DMARDs or TNFα inhibitors.