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ID PMID Title PublicationDate abstract
26892798 One year in review: ultrasound in arthritis. 2016 Jan Musculoskeletal ultrasound (MSUS) has become a relevant part of rheumatology practice and research because it substantially allows us to optimize management of rheumatic and musculoskeletal diseases. This non-invasive imaging modality is a valuable point-of-care tool to accurately evaluate intra-articular and periarticular structures involved in a wide range of rheumatic diseases in adults and children. In addition, MSUS is an invaluable bedside aid for guiding accurate and safe musculoskeletal aspirations, injections and biopsies. This review provides an overview of the literature of the last year on the role of MSUS in arthritis.
26956472 IL-10-Expressing Th2 Cells Contribute to the Elevated Antibody Production in Rheumatoid Ar 2016 Jun Rheumatoid arthritis (RA) is a common autoimmune disease associated with progressive disability, systemic complications, and early death. Multiple lines of evidence have placed adaptive immune responses in the center of RA pathogenesis. However, the functional roles of T helper cells are insufficiently described. Here, we examined the Th2 cell subsets and their functions in RA patients. A downregulation of IL-4(+) cells in CD4(+) T cells were observed in RA patients, indicating a downregulation of Th2 cells, and these results were confirmed by using and CXCR3 and CCR6 surface markers. We then found that CXCR3(-)CCR6(-) Th2 cells can be separated into IL-4(+) (single positive), IL-10(+) (single positive), and IL-4(+)IL-10(+) (double positive) subsets. Further results showed that CXCR5 only expressed on IL-10+ Th2 cells. The CXCR5(+) and CXCR5(-) Th2 cells each exhibited distinctive features in helping B cell antibody secretion. CXCR5(+) Th2 cells were more potent at stimulating total Ig and IgM secretion, while CXCR5(-) Th2 cells were more potent at stimulating IgE. IL-10 was required for helping B cell total Ig, IgM, and IgE production, while IL-4 was required for total Ig and IgE. The frequencies of IL-10(+) and IL-4(+)IL-10(+) Th2 cells were positively correlated with rheumatoid factor titer in vivo. Together, our study demonstrated distinctive subsets within Th2 cells, each with different impacts on antibody production and RA disease.
27427830 Baricitinib for the treatment of rheumatoid arthritis. 2016 Sep INTRODUCTION: Rheumatoid arthritis (RA) is characterized by systemic synovitis causing joint destruction. With the development of biological disease-modifying anti-rheumatic drugs (bDMARDs) and combination of conventional DMARDs, clinical remission is perceived as an appropriate and realistic goal in many patients. However, bDMARDs require intravenous or subcutaneous injection and some patients fail to respond to bDMARDs or lose their primary response. Under the circumstances, targeted synthetic DMARDs (tsDMARDs), which are orally available low-molecular weight products, have been emerging. Five phase 3 trials of Baricitinib, a JAK1 and JAK2 inhibitor, have been performed and showed high clinical efficacy in patients with active RA and naïve to sDMARDs or an inadequate response to sDMARDs, MTX or bDMARDs. There was a favorable response for clinical and functional parameters in studies with placebo, MTX and adalimumab as comparator. It is also reported that safety was tolerable within the limited study period. AREAS COVERED: We here review the recent progress in the development of baricitinib and its potential for the treatment of RA. Expert commentary: Although baricitinib is only one of the highly effective DMARDs that has a new mode of action, it will bring new concepts for rheumatology in the future.
24297378 The comparative effectiveness of abatacept versus anti-tumour necrosis factor switching fo 2015 Feb OBJECTIVE: We compared the effectiveness of abatacept (ABA) versus a subsequent anti-tumour necrosis factor inhibitor (anti-TNF) in rheumatoid arthritis (RA) patients with prior anti-TNF use. METHODS: We identified RA patients from a large observational US cohort (2/1/2000-8/7/2011) who had discontinued at least one anti-TNF and initiated either ABA or a subsequent anti-TNF. Using propensity score (PS) matching (n:1 match), effectiveness was measured at 6 and 12 months after initiation based on mean change in Clinical Disease Activity Index (CDAI), modified American College of Rheumatology (mACR) 20, 50 and 70 responses, modified Health Assessment Questionnaire (mHAQ) and CDAI remission in adjusted regression models. RESULTS: The PS-matched groups included 431 ABA and 746 anti-TNF users at 6 months and 311 ABA and 493 anti-TNF users at 12 months. In adjusted analyses comparing response following treatment with ABA and anti-TNF, the difference in weighted mean change in CDAI (range 6-8) at 6 months (0.46, 95% CI -0.82 to 1.73) and 12 months was similar (-1.64, 95% CI -3.47 to 0.19). The mACR20 responses were similar at 6 (28-32%, p=0.73) and 12 months (35-37%, p=0.48) as were the mACR50 and mACR70 (12 months: 20-22%, p=0.25 and 10-12%, p=0.49, respectively). Meaningful change in mHAQ was similar at 6 and 12 months (30-33%, p=0.41 and 29-30%, p=0.39, respectively) as was CDAI remission rates (9-10%, p=0.42 and 12-13%, p=0.91, respectively). CONCLUSIONS: RA patients with prior anti-TNF exposures had similar outcomes if they switched to a new anti-TNF as compared with initiation of ABA.
27028261 Alcohol use and menopause. 2016 Apr Clinicians should periodically assess their menopausal patients' alcohol use. Specific health hazards from excessive alcohol consumption, as well as potential benefits of low-level consumption (for cardiovascular disease, bone health, and type 2 diabetes), should be discussed with their patients who drink. The information in this Practice Pearl can help clinicians provide evidence-based guidance about alcohol consumption and its relationship to common health concerns.
26094771 Expression of anti-Porphyromonas gingivalis peptidylarginine deiminase immunoglobulin G an 2016 Feb BACKGROUND AND OBJECTIVE: Autoimmunity against citrullinated proteins through peptidylarginine deiminase (PAD) may be involved in the pathophysiology of rheumatoid arthritis (RA). The present study evaluated the serum levels of antibodies to citrullinated proteins and to Porphyromonas gingivalis PAD (PPAD), and the endogenous expression of PAD-4, in individuals with and without RA, as well as before and after periodontal treatment. MATERIAL AND METHODS: The study participants consisted of 52 patients with RA (RA group) and 26 age-, gender- and smoking status-matched healthy controls (non-RA group). Of the 52 patients, 26 were randomly assigned to receive oral hygiene instruction and supragingival scaling (RA subgroup). After periodontal and rheumatologic assessments, the serum levels of anti-cyclic citrullinated peptide (CCP) immunoglobulin G (IgG), anti-PPAD IgG and PAD-4 were determined using ELISA. RESULTS: The serum levels of anti-CCP IgG and anti-PPAD IgG were significantly higher in the RA group than in the non-RA group (p < 0.001 and p = 0.03). A significant, positive correlation was observed between the serum levels of anti-PPAD IgG and anti-CCP IgG (p = 0.04), but not between the serum levels of PAD-4 and anti-CCP IgG. Multiple logistic regression analyses revealed a significant association between anti-PPAD IgG responses and RA after adjustment for age, gender and smoking (p = 0.004). Supragingival scaling significantly improved the periodontal condition and disease activity of RA (p < 0.05), but failed to decrease the serum levels of anti-CCP IgG, anti-PPAD IgG and PAD-4 after 2 mo of treatment. CONCLUSION: These results might suggest an association between anti-PPAD IgG and anti-CCP IgG responses, implicating a role for PPAD in protein citrullination in patients with RA and periodontitis.
25787991 Quantitative analysis of cadherin-11 and β-catenin signalling during proliferation of rhe 2015 Aug OBJECTIVES: Cadherin-11 (CDH11) is an adhesion molecule that anchors β-catenin and is involved with various functions of synovial fibroblast cells (SFCs) during the development of rheumatoid arthritis (RA). However, the mechanism of CDH11 during RA-SFC proliferation is unclear. The aim of our study was to clarify the involvement of CDH11 and β-catenin signalling during proliferation. METHODS: IL-1β-induced and tumour necrosis factor-α (TNF-α)-induced cell proliferation, with CDH11 siRNAs, β-catenin-specific siRNAs and a CDH11-neutralizing antibody, were assessed by 5-Bromo-2'-deoxy-uridine ELISA. KEY FINDINGS: Using CDH11 siRNAs, there were a 42% reduction in IL-1β-induced proliferation and a 64% reduction in β-catenin protein. When β-catenin siRNAs were applied, there was a 63% reduction in IL-1β-induced proliferation. The median effective concentration (EC50 ) values for IL-1β-induced proliferation via CDH11-mediated β-catenin-dependent, total β-catenin-dependent and β-catenin-independent signalling were 0.0015, 0.016 and 0.18 ng/ml, respectively. Blocking CDH11 ligation with a CDH11-neutralizing antibody did not decrease IL-1β-induced proliferation. CONCLUSIONS: CDH11-mediated β-catenin signalling was 42% involved in IL-1β-induced proliferation and had the highest susceptibility to IL-1β among the proliferative signallings analysed in this study. The mode of action for CDH11 during the cell proliferation was likely associated with a pool of β-catenin protein. In contrast, CDH11 and β-catenin were not involved in TNF-α-induced RA-SFC proliferation.
25560583 Myelosuppressive and hepatotoxic potential of leflunomide and methotrexate combination in 2015 Feb BACKGROUND: Safety of the combination of leflunomide and methotrexate was examined in several studies with inconclusive results. The present study was designed to compare the efficacy and safety of the combination of leflunomide and methotrexate in adjuvant-induced arthritis (AIA) in rats focusing on immunosuppressive and hepatotoxic effects. METHODS: Eighty four rats were divided into seven groups. Group 1: Sham control, group 2: the vehicle control, group 3: methotrexate group, group 4-5: leflunomide (5 and 10mg/kg/day) groups, group 6-7: combination 1 and 2 [methotrexate+leflunomide (5 and 10mg/kg/day)] groups, respectively. RESULTS: The current results indicated that combination therapies improved the ankle circumference and clinical scores compared to monotherapies; histopathological examination confirmed these findings. The myelosuppressive effect of leflunomide (10mg/kg/day) was comparable to that produced by methotrexate as indicated by the complete blood count and bone marrow cellularity; however their combination resulted in greater toxicity. Furthermore, methotrexate greatly affected the splenic histopathology compared to leflunomide and the combination therapy produced a greater effect compared to leflunomide not methotrexate. Differently, assessment of the hepatotoxic potential of the two drugs highlighted that leflunomide induced a dose-dependent increase in the fibrosis score which was higher in their magnitude than that induced by methotrexate. Leflunomide (10mg/kg/day) and combination 2 groups showed the greatest degree of liver fibrosis. CONCLUSIONS: In rats with AIA, current drug combinations provided higher therapeutic benefit compared to monotherapies, however, greater toxicities were observed. Therefore, continuous monitoring of hematologic parameters and liver function will be recommended in clinical settings.
25707477 Efficacy and Safety of Anti-Interleukin-20 Monoclonal Antibody in Patients With Rheumatoid 2015 Jun OBJECTIVE: Interleukin-20 (IL-20) is implicated in the pathogenesis of rheumatoid arthritis (RA). The efficacy, safety, and tolerability of NNC0109-0012, a selective anti-IL-20 recombinant human monoclonal antibody (mAb), were assessed in patients with active RA who had an inadequate response to methotrexate therapy. METHODS: Sixty-seven patients with RA were enrolled and randomized (2:1) to receive NNC0109-0012 (3 mg/kg per week, subcutaneously) or placebo in a phase IIa, double-blind, 12-week trial with a 13-week followup. The primary end point was change in the Disease Activity Score in 28 joints based on C-reactive protein level (DAS28-CRP) from baseline to week 12. RESULTS: In patients treated with NNC0109-0012, the primary end point, improvement in the DAS28-CRP at week 12, was achieved (estimated difference -0.88; P = 0.02), with significant improvement starting at week 1. A greater response was observed in seropositive patients (estimated difference -1.66; P < 0.001), which was sustained through 13 weeks of followup, whereas no improvement was noted in patients with seronegative RA. A significant proportion of patients with seropositive RA receiving NNC0109-0012, compared to those receiving placebo, achieved treatment responses according to the American College of Rheumatology 20% (ACR20) (59% versus 21%), ACR50 (48% versus 14%), and ACR70 (35% versus 0%) levels of improvement, and showed greater improvements in the Health Assessment Questionnaire disability index (P = 0.047). The most frequent adverse events reported with NNC0109-0012 were injection site reactions and infections (e.g., herpes, nasopharyngitis, respiratory, and urinary). No serious infections or discontinuations associated with NNC0109-0012 were observed. CONCLUSION: In this phase IIa trial, treatment with NNC0109-0012 (anti-IL-20 mAb) was effective in patients with seropositive RA as early as week 1, with further improvements to week 12. No safety or tolerability concerns were identified with weekly NNC0109-0012 administration.
25526976 Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations fo 2015 Jul OBJECTIVE: The aim of this study was to establish guidelines for the optimization of biologic therapies for health professionals involved in the management of patients with RA, AS and PsA. METHODS: Recommendations were established via consensus by a panel of experts in rheumatology and hospital pharmacy, based on analysis of available scientific evidence obtained from four systematic reviews and on the clinical experience of panellists. The Delphi method was used to evaluate these recommendations, both between panellists and among a wider group of rheumatologists. RESULTS: Previous concepts concerning better management of RA, AS and PsA were reviewed and, more specifically, guidelines for the optimization of biologic therapies used to treat these diseases were formulated. Recommendations were made with the aim of establishing a plan for when and how to taper biologic treatment in patients with these diseases. CONCLUSION: The recommendations established herein aim not only to provide advice on how to improve the risk:benefit ratio and efficiency of such treatments, but also to reduce variability in daily clinical practice in the use of biologic therapies for rheumatic diseases.
27974302 Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis 2017 Jun OBJECTIVE: In rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray. METHODS: Pooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses. RESULTS: Progression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively). CONCLUSIONS: Early changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs.
27689735 Baricitinib in patients with inadequate response or intolerance to conventional synthetic 2017 Jan BACKGROUND: Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor. METHODS: In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3. RESULTS: More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein. CONCLUSIONS: In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage. TRIAL REGISTRATION NUMBER: NCT01721057; Results.
27084724 Economic Burden of Switching to a Non-Tumor Necrosis Factor Inhibitor Versus a Tumor Necro 2016 May INTRODUCTION: The objective of this study was to examine healthcare resource utilization (HRU) and costs associated with switching to another tumor necrosis factor alpha inhibitor (TNFi) therapy versus a non-TNFi therapy among patients with rheumatoid arthritis (RA) discontinuing use of an initial TNFi biologic therapy. METHODS: Patients with ≥2 RA diagnoses who used ≥1 TNFi on or after their initial RA diagnosis were identified in a US employer-based insurance claims database. Patients were selected based on ≥1 claim of another TNFi or a non-TNFi biologic therapy (occurring after 2010, and within 30 days before to 60 days after discontinuation of the initial TNFi), and continuous insurance ≥6 months before (baseline period) and ≥12 months after the switch date (study period). Patient demographic and clinical characteristics were measured during the baseline period. All-cause and RA-related HRU and costs were analyzed during the 12-month study period using multivariable regression analysis controlling for baseline characteristics and selected comorbidities. RESULTS: Of the 1577 patients with RA that switched therapies, 1169 patients used another TNFi and 408 patients used a non-TNFi biologic. The most commonly used initial TNFi treatments were etanercept (50%) and adalimumab (34%) among the TNFi cohort, and infliximab (39%) and etanercept (28%) among the non-TNFi cohort. The TNFi cohort had significantly fewer outpatient visits [all-cause: 23.01 vs. 29.77 visits/patient/year; adjusted incidence rate ratio (IRR) = 0.78, P < 0.001; RA-related: 7.42 vs. 13.58; adjusted IRR = 0.58, P < 0.001] and rheumatologist visits (all-cause: 4.01 vs. 6.81; adjusted IRR = 0.66, P < 0.001; RA-related: 3.23 vs. 6.40; adjusted IRR = 0.58, P < 0.001) than the non-TNFi cohort. All-cause total costs were significantly lower for patients who switched to another TNFi instead of a non-TNFi therapy ($36,932 vs. $44,566; adjusted difference = $7045, P < 0.01), as were total RA-related costs ($26,973 vs. $31,735; adjusted difference = $4904, P < 0.01). CONCLUSION: Adult patients with RA discontinuing TNFi therapy who switched to an alternative TNFi incurred lower healthcare costs than patients who switched to a non-TNFi biologic. FUNDING: AbbVie, Inc.
27562793 P2X7 receptor-mediated TG2 externalization: a link to inflammatory arthritis? 2017 Mar Transglutaminases have important roles in stabilizing extracellular protein assemblies in tissue repair processes but some reaction products can stimulate immune activation, leading to chronic inflammatory conditions or autoimmunity. Exacerbated disease in models of inflammatory arthritis has been ascribed to sustained extracellular enzyme activity alongside formation of select protein modifications. Here, we review the evidence, with a focus on the link between P2X7R signaling and TG2 export, a pathway that we have recently discovered which ties extracellular protein modifications into the danger signal-mediated innate immune response. These recent insights offer new opportunities for therapeutic intervention.
26482544 Interleukin-21 Induces Proliferation and Proinflammatory Cytokine Profile of Fibroblast-li 2016 Jan Fibroblast-like synoviocytes (FLS) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA) through aggressive proliferation and invasion, and certain proinflammatory cytokines may affect synoviocyte proliferation. To evaluate whether interleukin-21 (IL-21) could promote proliferation and proinflammatory cytokine production by RA-FLS, immunohistochemistry and immunoblotting were performed to observe the expression of IL-21 receptor (IL-21R) in synovial tissues and FLS from RA and osteoarthritis (OA) patients. The MTS assay was used to analyse RA-FLS proliferation. The concentrations of IL-6 and tumour necrosis factor-α (TNF-α) in culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). The signalling pathways triggered by IL-21 were characterized by immunoblotting. IL-21R was upregulated in the synovial tissues and FLS of RA patients as compared with OA patients. IL-21 stimulated RA-FLS proliferation and promoted the production of TNF-α and IL-6 and blockade of IL-21/IL-21R pathway with IL-21R.Fc attenuated IL-21-induced proliferation and secretion of TNF-α and IL-6. Moreover, IL-21 induced activation of the ERK1/2, PI3K/AKT and STAT3 pathways, and blockade of these pathways attenuated IL-21-induced proliferation and secretion of TNF-α and IL-6. These results suggest that IL-21 could promote RA-FLS proliferation and production of proinflammatory cytokines. Therefore, therapeutic strategies targeting IL-21 might be effective for the treatment of RA.
27372078 Influenza and pneumococcal vaccination in patients with rheumatoid arthritis in comparison 2016 Sep The aim of this study was to assess the vaccination status for influenza and pneumonia and the prevalence of hospitalised pneumonia in rheumatoid arthritis (RA) patients and population controls in Germany. Members of a large statutory health insurance fund in Germany who were continuously insured between 2009 and 2013 and had a diagnosis of RA in 2013 were age and sex matched 1:5 to members without RA. Pneumococcal and influenza vaccinations were evaluated with regard to age, sex and region of residence. Logistic regression models were used to determine predictors for influenza vaccination in RA patients. Prevalences of pneumonia that required hospitalisation were compared to regional vaccination rates. The data of 111,482 RA patients and 557,410 matched controls were available for analysis. Compared to controls, RA patients were vaccinated more frequently against influenza (40.8 vs. 32.2 %) and pneumonia (15.0 vs. 10.0 %). Vaccination rates increased with older age and differed between the federal states (highest in East Germany, lowest in South Germany). The region of residence, comorbidities, rheumatologic care and biologic treatment was associated with a higher probability of an influenza vaccination. Prevalences of pneumonia that required hospitalisation were 2-3 times higher in patients compared to controls and tended to be higher in regions with low vaccination rates. The increased pneumonia prevalence in RA patients confirms their status as a risk group. RA patients are vaccinated more frequently than controls, but vaccination rates are still low. The lower pneumonia prevalence in East Germany indicates that vaccination may help to reduce pneumonia in RA.
28535889 Unbalanced expression of aryl hydrocarbon receptor in peripheral blood CCR6(+)CD4(+) and C 2017 May OBJECTIVE: The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6(+)CD4(+) and CD4(+)CD25(+)T cells of patients with rheumatoid arthritis. METHODS: Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6(+)CD4(+)T, CD4(+)CD25(+)T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR. RESULTS: The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23±10.71)% vs. (18.83±7.32)%, p<0.01]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71±1.63) vs. (2.00±1.27), p=0.002; (2.62±2.08) vs. (0.62±0.29), p<0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4(+)CD25(+)T cells was significantly lower than that from controls [17.90 (6.10±80.10)% vs. (52.49±19.18)%, p<0.01]; In healthy controls, the percentage of AhR positive cells in CD4(+)CD25(+)T cells was significantly higher than that in CCR6(+)CD4(+)T cells, and was also significantly higher than that in PBMCs [(52.49±19.18)% vs. (23.18±5.62)% vs. (18.06±7.80)%, X(2)=24.03, p<0.01]; in RA patients, the percentage of AhR positive cells in CCR6(+)CD4(+)T cells was significantly increased than that in CD4(+)CD25(+)T cells and PBMCs [(46.02±14.68)% vs. 17.90 (6.10±80.10)% vs. (34.22±10.33)%, X(2)=38.29, p<0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6(+)CD4(+)T and CD4(+)CD25(+)T cells. CONCLUSION: AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood.
27213221 Tumour markers in rheumatoid arthritis-associated interstitial lung disease. 2016 Jul OBJECTIVES: Interstitial lung disease (ILD) is the most common pulmonary extra-articular manifestations of rheumatoid arthritis (RA), but the pathogenesis of RA-ILD is unknown. The purpose of this study was to investigate the tumour markers levels in patients of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to explore the diagnostic value of serum tumour markers for RA-ILD. METHODS: Twenty-eight patients with RA-ILD and 83 patients with RA only were included. Serum levels of tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 15-3, CA125, and CA19-9 were measured. RESULTS: Tumour markers CA15-3, CA125 and CA19-9 were increased in RA-ILD patients compared with RA without ILD patients. Logistic regression analysis revealed that older age (OR=1.06, 95% CI=[1.02-1.11]) and higher CA125 (OR=1.03, 95% CI=[1.01-1.05]) related to the increased risk of RA-ILD. ROC curve analysis showed the relationship between CA125 and RA-ILD was moderate (area under ROC curve (AUC)=0.78, 95% CI=[0.68-0.88]). In addition, CA125 levels above the normal reference (<35 U/ml) raised the risk of RA-ILD (OR=6.00, 95% CI=[2.37-15.16]). CONCLUSIONS: RA patient with older age and elevated tumour markers especially CA125 levels should be evaluated to check whether there is a potential of ILD.
25267562 Patient expectations and long-term outcomes in rheumatoid arthritis patients: results from 2015 Apr Little evidence exists to understand the influence of patient expectations on outcomes for silicone metacarpophalangeal arthroplasty (SMPA). The purpose of this paper is to compare long-term treatment outcome experiences regarding hand function/appearance for a surgical and nonsurgical cohort of rheumatoid arthritis (RA) patients and contrast them to expectations at baseline. This sample is part of a larger multicenter prospective cohort study of RA patients enrolled from 2004 to 2008. A total of 169 RA patients with severe deformities at the metacarpophalangeal (MCP) joints were recruited in the original study. Expectations for SMPA were collected at enrollment. A follow-up patient-reported questionnaire was completed at long-term follow-up. Baseline expectation questionnaires were collected from 137 patients, and follow-up data from 84 patients (average 6.7 years follow-up). At baseline, a significantly higher percent of patients who chose surgery expected to do "Anything I want" or "More activities than I do now" 1 year from enrollment than those who chose nonsurgical treatment. At follow-up, surgical patients remained more likely to indicate that they were currently able to do "Anything" or "More activities" than nonsurgical patients. A higher percentage of surgical patients were "very satisfied" or "quite satisfied" with their treatment compared to nonsurgical patients. RA subjects who chose SMPA reported greater expectations for surgery prior to surgery and also greater levels of hand function and satisfaction at long-term follow-up.
25651822 A store-operated calcium channel inhibitor attenuates collagen-induced arthritis. 2015 Jun BACKGROUND AND PURPOSE: Store-operated calcium (SOC) channels are thought to play a critical role in immune responses, inflammatory diseases and chronic pain. The aim of this study was to explore the potential role and mechanisms of SOC channels in collagen-induced arthritis (CIA). EXPERIMENTAL APPROACH: The CIA mouse model was used to examine the effects of the SOC channel inhibitor YM-58483 on CIA and arthritic pain. Hargreaves' and von Frey hair tests were conducted to measure thermal and mechanical sensitivities of hind paws. elisa was performed to measure cytokine production, and haematoxylin and eosin staining was used to assess knee histological changes. Western blot analysis was performed to examine protein levels. KEY RESULTS: Pretreatment with 5 or 10 mg · kg(-1) of YM-58483 reduced the incidence of CIA, prevented the development of inflammation and pain hypersensitivity and other signs and features of arthritis disease. Similarly, treatment with YM-58483 after the onset of CIA: (i) reversed the clinical scores; (ii) reduced paw oedema; (iii) attenuated mechanical and thermal hypersensitivity; (iv) improved spontaneous motor activity; (v) decreased periphery production of IL-1β, IL-6 and TNF-α; and (vi) reduced spinal activation of ERK and calmodulin-dependent PKII (CaMKIIα). CONCLUSIONS AND IMPLICATIONS: This study provides the first evidence that inhibition of SOC entry prevents and relieves rheumatoid arthritis (RA) and arthritic pain. These effects are probably mediated by a reduction in cytokine levels in the periphery and activation of ERK and CaMKIIα in the spinal cord. These results suggest that SOC channels are potential drug targets for the treatment of RA.