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ID PMID Title PublicationDate abstract
28823567 Participants' experiences of an Education, self-management and upper extremity eXercise Tr 2017 Dec BACKGROUND: The Education, self-management and upper extremity eXercise Training for people with Rheumatoid Arthritis programme (EXTRA) is an individualized, upper limb, home exercise regimen supplemented by four supervised, group sessions, a handbook and exercise dairy which improves upper extremity disability and self-efficacy. OBJECTIVE AND STUDY DESIGN: This qualitative interview study explored participants' experience of EXTRA to inform development and implementation of EXTRA into practice. PARTICIPANTS: Adults with Rheumatoid Arthritis who completed EXTRA were purposively sampled to include a range of ages, upper extremity disabilities, self-efficacy for arthritis self-management and attendance at EXTRA sessions. METHODS: Individual, semi-structured interviews were conducted with a single researcher until data saturation of themes was reached. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Twelve participants (10 females; 32 to 87 years) were interviewed. Four overarching themes were identified: (i) empowering self-management; (ii) influence of others and (iii) the challenge of sustaining exercise, which resonate with the Social Cognition Theory, and (iv) refining EXTRA: consistent and personalised. CONCLUSIONS: EXTRA enhanced participants' confidence to manage their arthritis independently and was adaptable so it could be integrated with other life commitments. Whilst healthcare professionals, peers and family and friends influenced exercise uptake, sustaining exercise was challenging. Participants desired consistent and continuing contact with a familiar physiotherapist (e.g. via follow-up appointments, digital health technologies) which accommodated individual needs (e.g. different venues, session frequency). Implementation of EXTRA needs to appreciate and address these considerations to facilitate success.
25802019 Glucocorticoid safety for treating rheumatoid arthritis. 2015 Jun INTRODUCTION: Glucocorticoids (GCs) are often used in the treatment of rheumatoid arthritis and many other inflammatory diseases. Besides strong favorable effects on disease activity, GCs can cause (serious) side effects as well. AREAS COVERED: Side effects of GCs that are ranked as most important by rheumatologists as well as by patients are bone loss and fractures, cardiovascular events, hypertension, and diabetes mellitus. In evaluating these side effects, confounding by indication is a disturbing factor: not only the use of GCs can increase the risk of several side effects, but so can the activity of the underlying disease, which in turn is related to the amount of GCs that is prescribed to the patient. EXPERT OPINION: Generally, side effects predominantly occur in patients with a high disease activity and when used in high doses and for a long period of time. For these patients, caution and monitoring are most warranted. However, monitoring is not only recommended in patients with a high disease activity, and high-dose or long-term use of GCs, but in all GC users, since side effects may also occur in patients treated with low-dose GCs. When detecting possible negative effects in time, they might be managed and serious damage due to side effects might hopefully be prevented.
27594920 Prevalence of foot problems in people with inflammatory arthritis in Singapore. 2016 BACKGROUND: Foot problems are highly prevalent in people with inflammatory arthritis reported from studies in the UK, Europe and New Zealand, but there is limited evidence from Southeast Asia. The study aim was to evaluate the prevalence of foot problems in people with inflammatory arthritis in Singapore. METHODS: People with inflammatory arthritis were recruited from the rheumatology outpatient clinic of a tertiary hospital in Singapore. Disease and clinical characteristics included age, sex, disease duration, current blood tests and medications. The Leeds Foot Impact Scale was used to evaluate foot impairment/disability and the Modified Health Assessment Questionnaire was used to assess global function. RESULTS: We recruited 101 people with inflammatory arthritis, of which 50 % were female. The majority of participants were Chinese (70 %). The mean (SD) age was 52 (15) years, and the mean (SD) disease duration was 9.3 (0.3) years. The most commonly reported inflammatory arthritic conditions were rheumatoid arthritis (46), gout (31) and spondyloarthritis (15 %). The mean (SD) of the total Leeds Foot Impact Scale was 17 (13) indicating moderate to severe levels of foot impairment and activity limitation. Over 80 of participants reported foot pain during the course of their condition, and 48 % reported current foot pain. Despite the high prevalence of foot pain, only 21 participants (21 %) had been referred to a podiatrist. CONCLUSION: This is the first study to investigate the prevalence of foot problems in people with inflammatory arthritis from Singapore. The majority of the participants reported foot problems, but had not been referred to a podiatry service.
25747348 Rheumatoid arthritis: Perioperative management of biologics and DMARDs. 2015 Jun OBJECTIVE: Arthroplasty remains prevalent for patients with rheumatoid arthritis (RA), but outcomes are not equivalent to patients with osteoarthritis, and complications including infection are increased. The objective of this article is to review the current evidence supporting perioperative medication management. Challenges are discussed such as continuing potent disease-modifying therapy (DMARDs) and biologics, which may increase infection risk, versus withholding these medications, which may result in disease flares. METHODS: Published literature regarding arthroplasty in RA has been reviewed and discussed. RESULTS: Some DMARDs such as methotrexate and hydroxychloroquine appear safe in the perioperative period. Anti-TNFα biologics should be withheld due to increase in infection risk, while the impact of rituximab and abatacept on infection risk has not been as clearly defined. CONCLUSION: This article provides an overview of arthroplasty in RA, summarizes the evidence supporting perioperative medication management including corticosteroids, and identifies areas where further study is needed.
26511098 Acute Hepatitis E Virus infection with coincident reactivation of Epstein-Barr virus infec 2015 Oct 29 BACKGROUND: Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA). CASE PRESENTATION: A 68-year-old Swiss woman with RA developed hepatitis initially diagnosed as methotrexate-induced liver injury, but later diagnosed as autochthonous HEV infection accompanied by reactivation of her latent EBV infection. She showed confounding serological results pointing to three hepatotropic viruses (HEV, Hepatitis B virus (HBV) and EBV) that could be resolved by detection of HEV and EBV viraemia. The patient recovered by temporary discontinuation of immunosuppressive therapy. CONCLUSIONS: In immunosuppressed patients with RA and signs of liver injury, HEV infection should be considered, as infection can be treated by discontinuation of immunosuppression. Although anti-HEV-IgM antibody assays can be used as first line virological tools, nucleic acid amplification tests (NAAT) for detection of HEV RNA are recommended--as in our case--if confounding serological results from other hepatotropic viruses are obtained. After discontinuation of immunosuppressive therapy, our patient recovered from both HEV infection and reactivation of latent EBV infection without sequelae.
24431393 Evaluating processes underlying the predictive value of baseline erosions for future radio 2015 May OBJECTIVES: Baseline erosions are characteristic for rheumatoid arthritis (RA) and predictive for a severe disease course. The mechanisms leading to baseline erosions being a strong predictor for radiological progression are unknown. We aimed to increase this understanding by mediation analyses in an observational cohort and a cross-sectional MRI study. METHODS: 3256 hands and feet radiographs of 653 early RA patients assessed during 7 years of disease were scored using the Sharp-van der Heijde method. Mediation models and multivariate regression analyses were used to explore the association between baseline erosions, other predictors and radiological damage over time. 603 joints (MCP2-5 and MTP1-5) of 67 RA patients underwent 1.5 T MRI at baseline. Data on MRI inflammation were compared with clinical inflammation and baseline radiological erosions. RESULTS: Patients with baseline erosions had, at any point in time during 7 years, 3.45 times more joint damage than patients without erosions (p<0.001, 95% CI 3.00 to 3.98). Baseline erosions were an independent predictor and not a mediator between symptom duration, systemic or local clinical inflammation (erythrocyte sedimentation rate (ESR), swollen joint count (SJC)) or autoantibodies (anti-citrullinated-peptide antibodies, rheumatoid factor) and radiological damage. Subclinical MRI inflammation was studied in relation to erosions, revealing that 83% of the non-swollen joints with baseline erosions had subclinical MRI inflammation compared with 25% of the non-swollen joints without baseline erosions (OR 15.2 95% CI 3.1 to 102.1). The association between MRI inflammation and baseline erosions was independent of symptom duration, ESR, SJC and autoantibodies. CONCLUSIONS: Baseline erosions are a predictor for future joint damage, independent of known predictors as time, autoantibodies or clinical measurable inflammation. Subclinical inflammation is suggested as an underlying mechanism.
24927637 Methotrexate-associated lymphoproliferative disorders of the tongue developing in patients 2015 Jan Incidences of lymphoproliferative disorders (LPDs) in patients with compromised immune systems associated with immunosuppressants such as methotrexate (MTX) administered for the treatment of rheumatoid arthritis (RA) are reportedly increasing. Although extranodal lesions develop in half of the patients with MTX-associated LPDs, only a few studies have reported on intraoral lesions. We evaluated 2 elderly women with MTX-associated LPDs who had received MTX for the treatment of RA and presented with atypical ulceration of the tongue. Biopsy specimens demonstrated polymorphous B-cell LPD, probably associated with MTX. Epstein-Barr virus (EBV) was identified by immunohistochemistry for latent membrane protein 1 and by EBV-encoded RNA in situ hybridization. After MTX withdrawal, in both cases, ulcers showed complete regression at 8 weeks, and no subsequent treatment was required. Close monitoring of LPDs is mandatory, because recurrence within 10 months has been reported in half of the patients in whom LPDs had initially regressed.
26395832 Scientific rationale behind the development and approval of biosimilar infliximab (CT-P13) 2015 Biosimilars are drugs developed to be highly similar to their originator biologic (or 'reference medicinal product') with no clinically meaningful differences in purity, efficacy or safety. Production of biologics and biosimilars is highly complex and sensitive, with any change in manufacturing process having a potential impact on efficacy and safety. This review provides an overview of the manufacturing process for these drugs and considers the implications of any process changes. The scientific rationale underlying the regulatory comparability exercise for process-changed reference medicinal products and biosimilars is also discussed, as is the issue of 'switchability' from a reference medicinal product to its biosimilar. CT-P13 (Remsima(®), Inflectra(®)), a biosimilar of infliximab, is used as a case study to discuss these issues.
24912961 Interrelated reduction of chemerin and plasminogen activator inhibitor-1 serum levels in r 2015 Mar Inflammatory/metabolic factors and imbalance of haemostasis contribute to cardiovascular disease risk in rheumatoid arthritis (RA). Interleukin-6 (IL-6), a cytokine that plays an important role in immune responses, is implicated in its pathogenesis. In this study, the effects of the IL-6 receptor inhibitor, tocilizumab, on serum adipokines and coagulation/fibrinolysis factors in RA patients were examined. Nineteen consecutive patients (18 women, aged 48 ± 9 years) received six monthly infusions of 8 mg/kg tocilizumab for moderate or severe RA. Disease activity/severity, as well as serum levels of chemerin apelin, plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), glucose, insulin and lipids were measured at baseline and at 1, 3 and 6 months thereafter. Chemerin and PAI-1 levels decreased significantly from baseline through 3 to 6 months (from 256 ± 79 to 174 ± 12 and 210 ± 85 ng/ml; from 73 ± 27 to 56 ± 22 and 51 ± 28 pg/ml, respectively). Other adipokines did not change, despite increases in adiposity. In multivariate models, significant independent associations were found between baseline chemerin with age, body mass index, remission of disease, HAQ-Di, CRP and PAI-1. Chemerin decrease at 6 months was significantly associated with PAI-1 and IL-6 changes at 6 months. Baseline PAI-1 associated negatively with remission of disease and total cholesterol, while PAI-1 change at 6 months associated with chemerin changes and smoking status. In conclusion, inhibition of IL-6 signaling in RA favorably alters chemerin and PAI-1 levels in an interrelated manner, despite increasing adiposity. This might represent a dual anti-inflammatory and anti-thrombotic/fibrinolytic mechanism of tocilizumab that may reduce cardiovascular event risk in RA patients.
27236390 Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response 2016 May BACKGROUND: Tocilizumab (TCZ) is a humanized anti-human IL-6R antibody, a novel therapy for rheumatoid arthritis (RA) patients who fail treatment with disease modifying anti-rheumatic drugs (DMARDs) or anti-tumor necrosis factor (anti-TNFs). OBJECTIVE: To assess the safety and efficacy of TCZ monotherapy or in combination with non-biologic DMARDs or anti-TNFs in moderate to severe active RA. DESIGN: Prospective, phase III, multi-center, open-label, single arm, 24-week trial. SETTING: Three centers in Saudi Arabia. PATIENTS AND METHODS: The study included consecutive RA patients infused with TCZ (8 mg/kg) over 60 minutes every 4 weeks (up to 6 times), either alone or with non-biologic DMARDs. Patients were followed for 24 weeks. Patients with good/moderate European League Against Rheumatism responses, continued on TCZ as long as commerically available or for 1 year. MAIN OUTCOME MEASURE(S): Disease activity measured by DAS28 score. RESULTS: Of 28 patients enrolled from 2 November 2011 to 12 May 2013 (18 months), 21 completed (77.8%) and 7 (25%) discontinued TCZ therapy. One patient was excluded from the intent-to-treat analysis. Efficacy analysis showed a significant difference (P < .0001) in the Disease Activity Score based on 28 joints and on swollen and tender joint counts. Three (10.7%) patients experienced at least one AE that was considered related to study drug (one probably and two possibly). Only one (3.6%) patient reported a severe adverse event (neutropenia and thrombocytopenia). No adverse events led to dose modification or death. CONCLUSION: TCZ monotherapy or in combination with non-biologic DMARDs resulted in a significant effect on the endpoints in moderate to severe RA in Saudi Arabia, which is consistent with other published reports. LIMITATIONS: No information on tapering of steroid therapy, lack of follow-up data of all 28 patients, lack of data on long-term effects of TCZ on lipid levels and the need for statins. (ClinicalTrials.gov identifier: NCT01326962).
25480531 [Intra-articular injections of triamcinolone hexacetonide in rheumatoid arthritis: short a 2015 May OBJECTIVES: Identify good response predictors to intra-articular injection (IAI) with triamcinolone hexacetonide (TH). METHODS: This study was carried out in rheumatoid arthritis (RA) patients (American College of Rheumatology criteria) submitted to IAI (mono, pauci or polyarticular injection). ASSESSMENT: A "blinded" observer prospectively evaluated joints at one week (T1), four weeks (T4), twelve weeks (T12) and 24 weeks (T24) after IAI. Outcome measurements included Visual Analogue Scale (0-10 cm) at rest, in movement and for swollen joints. Clinical, demographic and variables related to injection at baseline were analyzed according to IAI response. RESULTS: We studied 289 patients with RA (635 joints) with a mean age of 48.7 years (±10.68), 48.5% of them Caucasians, VAS for global pain=6.52 (±1.73). Under univariate analysis, the variables relating the best responses following IAI (improvement > 70%) were: "elbow and metacarpophalangeal (MCP) IAI, and functional class II". Under multivariate analysis, "males" and "non-whites" were the predictors with the best response to IAI at T4, while "elbow and MCP IAI", "polyarticular injection", "use of methotrexate" and "higher total dose of TH" obtained the best response at T24. CONCLUSION: Several predictors of good response to IAI in patients with RA were identified. The best-response predictors for TH IAI of long term were "apply elbow and MCP IAI" and "apply polyarticular injection".
27965246 Association of sleep duration with rheumatoid arthritis in Korean adults: analysis of seve 2016 Dec 13 OBJECTIVES: To investigate the association between rheumatoid arthritis (RA) and self-reported sleep duration. SETTING: The present study analysed 7 years of aggregated cross-sectional data (2007-2013) from the Korea National Health and Nutrition Examination Surveys (KNHANES). PARTICIPANTS: A total of 37 979 individuals were selected for the analyses. INTERVENTIONS: RA. PRIMARY AND SECONDARY OUTCOME MEASURES: Sleep duration. RESULTS: After adjusting for confounding factors, the odds of short-duration sleepers (≤6 hours/day) and long-duration sleepers (≥9 hours/day) for RA were 1.23-fold (95% CI 1.101 to 1.51) and 1.27-fold (95% CI 0.85 to 1.88) higher, respectively, than those for persons with sleep duration of 7-8 hours/day. A subgroup analysis according to the extent of pain in RA revealed that the strong relationship between RA and sleep disturbances was observed in those with high pain from RA (OR: 1.28 CI 1.04 to 1.58). CONCLUSIONS: Individuals with RA may be at a higher risk for sleep disturbances compared with individuals without RA. Therefore, the provision of comprehensive care for patients with RA by healthcare professionals should include assessments of sleep duration and patients with RA should be encouraged to report sleep problems.
28276212 Anti-cyclic citrullinated peptide antibodies are not frequently observed in children with 2016 Type 1 diabetes mellitus (DM) and rheumatoid arthritis (RA) have been reported to occur concurrently in some cases. This study aimed to evaluate the presence of anti-cyclic citrullinated peptide (CCP) antibodies, which have been reported to have diagnostic value for RA, in children with type 1 DM. The study included 90 children with type 1 DM (Group 1) and 76 control cases (Group 2). The rates of reported family histories of RA and rheumatoid factor positivity did not differ between groups. In group 1, one case (1.1%) was positive for anti-CCP antibodies, whereas none of the controls were positive. The anti-CCP positive patient had no relevant joint complaints. Anti-CCP antibodies were rarely found in cases of pediatric type 1 DM. Thus, relevant screening in the follow-up of pediatric patients does not appear to be rational in the absence of any signs or symptoms of arthritis. The single case exhibiting a high anti-CCP level needs to be followed up for RA, although this positive result might be nonspecific and transient.
27036883 Colony-stimulating factor (CSF) 1 receptor blockade reduces inflammation in human and muri 2016 Mar 31 BACKGROUND: CSF-1 or IL-34 stimulation of CSF1R promotes macrophage differentiation, activation and osteoclastogenesis, and pharmacological inhibition of CSF1R is beneficial in animal models of arthritis. The objective of this study was to determine the relative contributions of CSF-1 and IL-34 signaling to CSF1R in RA. METHODS: CSF-1 and IL-34 were detected by immunohistochemical and digital image analysis in synovial tissue from 15 biological-naïve rheumatoid arthritis (RA) , 15 psoriatic arthritis (PsA) and 7 osteoarthritis (OA) patients . Gene expression in CSF-1- and IL-34-differentiated human macrophages was assessed by FACS analysis and quantitative PCR. RA synovial explants were incubated with CSF-1, IL-34, control antibody (Ab), or neutralizing/blocking Abs targeting CSF-1, IL-34, or CSF1R. The effect of a CSF1R-blocking Ab was examined in murine collagen-induced arthritis (CIA). RESULTS: CSF-1 (also known as M-CSF) and IL-34 expression was similar in RA and PsA synovial tissue, but lower in controls (P < 0.05). CSF-1 expression was observed in the synovial sublining, and IL-34 in the sublining and the intimal lining layer. CSF-1 and IL-34 differentially regulated the expression of 17 of 336 inflammation-associated genes in macrophages, including chemokines, extra-cellular matrix components, and matrix metalloproteinases. Exogenous CSF-1 or IL-34, or their independent neutralization, had no effect on RA synovial explant IL-6 production. Anti-CSF1R Ab significantly reduced IL-6 and other inflammatory mediator production in RA synovial explants, and paw swelling and joint destruction in CIA. CONCLUSIONS: Simultaneous inhibition of CSF1R interactions with both CSF-1 and IL-34 suppresses inflammatory activation of RA synovial tissue and pathology in CIA, suggesting a novel therapeutic strategy for RA.
27997219 Real-world cost-effectiveness of infliximab for moderate-to-severe rheumatoid arthritis in 2017 May AIM: To assess the cost-effectiveness of infliximab-containing therapy (ICT) for moderate-to-severe rheumatoid arthritis (RA) in a medium-sized Chinese city. METHODS: A Chinese prospective cohort study comparing ICT (25 patients) versus conventional disease-modified antirheumatic drugs (24 patients) for RA was used to assess the cost-effectiveness of ICT. RESULTS: The cohort study observed significantly reduced disease activity score of 28 joints (coefficient -2.718, p < 0.001), improved EQ-5D (coefficient 0.453, p < 0.001) and increased medical costs (coefficient 1.289, p < 0.001) associated with ICT. The incremental cost-effectiveness ratio per gained quality-adjusted life year for ICT versus disease-modified antirheumatic drugs was 1.897-times of the local gross domestic product per capita. CONCLUSION: Infliximab was a favorable cost-effective alternative option for moderate-to-severe RA in a medium-sized city of China.
25599563 Associations between single-nucleotide polymorphisms of RFC-1, GGH, MTHFR , TYMS, and TCII 2015 INTRODUCTION: The differences in drug efficacy and adverse reactions may be caused by genetic variations in drug metabolism between individuals. OBJECTIVES: The aim of the study was to evaluate the effect of gene polymorphisms on the efficacy of therapy and side effects in patients with rheumatoid arthrit s (RA) treated with methotrexate (MTX). PATIENTS AND METHODS: A total of 273 Caucasian patients with RA were treated with MTX for at least 6 months or stopped MTX because of adverse effects. Seven polymorphisms (RFC-1 c.80G>A, GGH c.-401C>T, MTHFR c.1298A>C and c.677C>T, TYMS 2R/3R, TYMS 6-bp deletion, and TCII c.593T>C) were examined for their effects on MTX efficacy and toxicity. Genomic DNA was obtained from peripheral blood leukocytes. RESULTS: Of all patients, 53% reported some adverse effects during at least 1 visit, which led to MTX withdrawal in 17% of the patients. Adverse effects were more frequent in patients with the MTHFR 677T allele than in those with the 677CC genotype (odds ratio [OR], 1.97; P = 0.01) and in those with the GGH 401CC genotype than in those with the GGH 401CT and TT genotypes (OR, 3.8; P = 0.05). Furthermore, the MTHFR 677T allele was associated with increased activity of aminotransferases (OR, 3.4; P = 0.02). MTX-related hepatotoxicity and alopecia were more common in patients with the RFC-1 80AA genotype (OR, 3.5, P = 0.01; OR, 2.4, P = 0.04; respectively). A more rapid positive response to MTX therapy was demonstrated in MTHFR 677CC homozygotes (OR, 3.4; P = 0.001). There were no other associations between single -nucleotide polymorphisms and the efficacy of MTX treatment. CONCLUSIONS: The MTHFR 677CC and GGH 401TT and CT genotypes were associated with a reduction in the number of MTX-related adverse events. Future allele and genotype analyses may help identify the subsets of RA patients with an increased risk of adverse effects.
25879761 Differential expression of pro-inflammatory cytokines IL-15Ralpha, IL-15, IL-6 and TNFalph 2015 Mar 12 BACKGROUND: Pro-inflammatory cytokines are directly implicated in the pathogenesis of Rheumatoid arthritis (RA). Variable clinical response to cytokine targeted therapies as TNFalpha and IL-6, strongly highlights the heterogeneity of inflammatory process in RA. Another cytokine, IL-15 has also been related to the inflammatory process in RA. Recently we described for the first time, the presence of its specific receptor, IL-15Ralpha, in synovial fluid (SF). The aim of this work was to compare the expression profile of IL-15Ralpha, its ligand IL-15, TNFalpha and IL-6 and how these cytokines are correlated in SF from RA patients taking as a reference Osteoarthritis (OA), an articular but not autoimmune disease. METHODS: Synovial fluids were obtained from the knee joints of 60 patients, 30 with confirmed diagnosis of RA and 30 with OA diagnosis. The levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha were measured by ELISA. A statistical analysis was performed with GraphPad Prism v5.0 using the Mann-Whitney U test and Spearman's rank correlation. A cluster analysis was run in MeV software v4.9.0 and differences across clusters were evaluated by an ANOVA including post-test analysis. RESULTS: We found higher and significant levels of TNFalpha, IL-6 and IL-15Ralpha but not of IL-15 in RA compared with the OA group. Additionally, a high inter-individual variability in the levels of these 4 cytokines was observed in RA, although we identified 4 patients' subgroups by cluster analysis of cytokines concentration in SF. We also found a positive correlation between IL-15Ralpha-IL-6 and IL-15Ralpha-IL-15, but not for other pairs of cytokines in RA. In addition we found correlation between the value of IL-15Ralpha in SF and disease activity score, DAS28. CONCLUSIONS: In our current work we found a high inter-individual variability in the levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha in SF of RA patients and were identified four principal clusters of cytokines concentration in SF, suggesting the importance of identifying disease subset of patients for personalized treatment. Finally, we found a correlation between IL-15Ralpha-IL-6, IL-15Ralpha-IL-15, but we did not find any correlation between other pairs of studied cytokines in SF.
25261692 Aberrant CD200/CD200R1 expression and its potential role in Th17 cell differentiation, che 2015 Apr OBJECTIVE: CD200/CD200R1 signalling has an immunoregulatory effect on the activation threshold of the inflammatory immune response and maintains immune homeostasis. In this study we evaluated the status of CD200/CD200R1 interaction in patients with RA. METHODS: The expression of CD200 and CD200R1 was examined by immunohistochemistry and flow cytometry and was compared between RA patients and healthy controls (HCs). Sorted CD4(+) T cells were stained with carboxyfluorescein succinimidyl ester (CFSE) and annexin V-propidium iodide to evaluate the effect of CD200 on cell proliferation and apoptosis. The effect of CD200 on Th17 differentiation, function and osteoclastogenesis was determined by flow cytometry, transwell migration assay and immunocytochemistry, respectively. RESULTS: The proportion of CD200(+) cells and CD200R1(+) cells in peripheral blood mononuclear cells, peripheral CD14(+) cells and CD4(+) T cells was significantly lower in the RA patients than in HCs, whereas the number of CD200(+) cells was higher in synovium from RA patients than in that from HCs. After treatment with infliximab and MTX we found increased expression of peripheral CD200/CD200R1 that correlated with a decrease in the 28-joint DAS. CD200Fc in vitro partially inhibited CD4(+) T cell proliferation, promoted CD4(+) T cell apoptosis, reduced CD4(+) T cell differentiation into Th17 cells and down-regulated CCR6-mediated Th17 chemotaxis in cells from RA patients. In addition, the engagement of the CD200 receptors on CD14(+) cells with CD200Fc in vitro reduced osteoclastogenesis and inhibited CD14(+) cell-driven Th17 differentiation. CONCLUSION: Abnormal CD200/CD200R1 expression in RA may contribute to abnormal Th17 cell differentiation, chemotaxis and osteoclastogenesis.
27022991 Arthritis as a risk factor for carpal tunnel syndrome: a meta-analysis. 2016 Oct OBJECTIVES: The effects of inflammatory and degenerative arthritis on carpal tunnel syndrome (CTS) are not well known. This systematic review and meta-analysis aimed to assess whether rheumatoid arthritis (RA) and osteoarthritis (OA) increase the risk of CTS. METHOD: Literature searches were conducted in PubMed, Embase, Web of Science, Scopus, Google Scholar, and ResearchGate until January 2015. Twenty-three (five cohort, 10 case control, and eight cross sectional) studies qualified for the meta-analyses. A random-effects meta-analysis was used and heterogeneity and publication bias were assessed. RESULTS: Both RA and OA were associated with CTS. Pooled unadjusted odds ratios (ORs) were 1.91 [95% confidence interval (CI) 1.33-2.75, I(2) = 55.2%, nine studies, n = 10 688] for arthritis (either inflammatory or degenerative), 2.91 (95% CI 2.33-3.62, I(2) = 22.3%, 11 studies, n = 74 730) for RA, and 2.13 (95% CI 1.65-2.76, I(2) = 39.2%, five studies, n = 20 574) for OA of any joint. Pooled confounder-adjusted ORs were 1.96 (95% CI 1.21-3.18, I(2) = 73.1%, six studies, n = 11 542) for arthritis, 1.96 (95% CI 1.57-2.44, I(2) = 32.2%, eight studies, n = 72 212) for RA, and 1.87 (95% CI 1.64-2.13, I(2) = 0%, two studies, n = 19 480) for OA. There was no evidence of publication bias, and excluding cross-sectional studies or studies appraised as having a high risk of selection bias did not change the magnitude of the associations. CONCLUSIONS: The findings of this systematic review and meta-analysis suggest that both RA and OA increase the risk of CTS. Further prospective studies on the effect of wrist OA on CTS are needed.
27165430 Different expression of β subunits of the KCa1.1 channel by invasive and non-invasive hum 2016 May 10 BACKGROUND: Fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA-FLS) contribute to joint inflammation and damage characteristic of the disease. RA-FLS express KCa1.1 (BK, Slo1, MaxiK, KCNMA1) as their major plasma membrane potassium channel. Blocking KCa1.1 reduces the invasive phenotype of RA-FLS and attenuates disease severity in animal models of RA. This channel has therefore emerged as a promising therapeutic target in RA. However, the pore-forming α subunit of KCa1.1 is widely distributed in the body, and blocking it induces severe side effects, thus limiting its value as a therapeutic target. On the other hand, KCa1.1 channels can also contain different accessory subunits with restricted tissue distribution that regulate channel kinetics and pharmacology. Identification of the regulatory subunits of KCa1.1 expressed by RA-FLS may therefore provide the opportunity for generating a selective target for RA treatment. METHODS: Highly invasive RA-FLS were isolated from patients with RA, and FLS from patients with osteoarthritis (OA) were used as minimally invasive controls. The β subunit expression by FLS was assessed by quantitative reverse transcription polymerase chain reactions, Western blotting, and patch-clamp electrophysiology combined with pharmacological agents. FLS were sorted by flow cytometry on the basis of their CD44 expression level for comparison of their invasiveness and with their expression of KCa1.1 α and β subunits. β1 and β3 subunit expression was reduced with small interfering RNA (siRNA) to assess their specific role in KCa1.1α expression and function and in FLS invasiveness. RESULTS: We identified functional β1 and β3b regulatory subunits in RA-FLS. KCa1.1 β3b subunits were expressed by 70 % of the cells and were associated with highly invasive CD44(high) RA-FLS, whereas minimally invasive CD44(low) RA-FLS and OA-FLS expressed either β1 subunit. Furthermore, we found that silencing the β3 but not the β1 subunit with siRNA reduced KCa1.1 channel density at the plasma membrane of RA-FLS and inhibited RA-FLS invasiveness. CONCLUSIONS: Our findings suggest the KCa1.1 channel composed of α and β3b subunits as an attractive target for the therapy of RA.