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ID PMID Title PublicationDate abstract
29134512 Artery compliance in patients with rheumatoid arthritis: results from a case-control study 2018 Jan Atherosclerosis is one of the most common complications of rheumatoid arthritis (RA). The objective of this study is to evaluate differences in large artery compliance (C1) and small artery compliance (C2) between RA and controls and evaluating factors associated with reduced compliance in the RA population. The profiling of large and small arterial compliance was analyzed in 185 RA patients and 88 healthy controls using Cardiovascular Profiling Instrument. The correlations of arterial compliance and the relevant clinical data were determined in these subjects. Then correlation analysis and regression analysis were performed to find whether rheumatoid arthritis patients have more risk factors than healthy controls in artery compliance and to explore the possible element involved in RA patients including traditional cardiovascular risk factors, RA disease-related factors, and the therapy. Compared with healthy controls, levels of C1 and C2 were significantly decreased in RA patients. Having adjusted the traditional risk factors associated with atherosclerosis, C1 and C2 decline was still a significant indicator in RA patients [odds ratio = 7.411(95%CI 3.275, 16.771) and 10.184(95%CI 4.546, 22.817)]. Using multi-factor regression analysis to adjust traditional risk factors for arterial compliance, we found that the levels of ESR was correlated with the abnormal large artery compliance [odds ratio = 1.021(95%CI 1.007, 1.035)]. The HAQ values and the current usage of leflunomide were correlated with the abnormal small artery compliance in RA patients [odds ratio = 1.161(95%CI 1.046, 1.289) and 6.170(95%CI 1.510, 25.215)]. The values of C1 and C2 are indicators of artery compliance in RA patients. ESR, HAQ values, and the usage of leflunomide might be possible risk factors of artery compliance. The evaluation of artery compliance could be an easy and reliable test that could help us to screen and predict cardiovascular disorders in RA patients.
28621011 Yoga for the management of pain and sleep in rheumatoid arthritis: a pilot randomized cont 2018 Mar OBJECTIVE: The aim of the present study was to determine the feasibility of a relaxation-based yoga intervention for rheumatoid arthritis, designed and reported in accordance with Delphi recommendations for yoga interventions for musculoskeletal conditions. METHODS: Participants were recruited from a hospital database, and randomized to either eight weekly 75-min yoga classes or a usual care control. Feasibility was determined by recruitment rates, retention, protocol adherence, participant satisfaction and adverse events. Secondary physical and psychosocial outcomes were assessed using self-reported questionnaires at baseline (week 0), week 9 (primary time point) and week 12 (follow-up). RESULTS: Over a 3-month period, 26 participants with mild pain, mild to moderate functional disability and moderate disease activity were recruited into the study (25% recruitment rate). Retention rates were 100% for yoga participants and 92% for usual care participants at both weeks 9 and 12. Protocol adherence and participant satisfaction were high. Yoga participants attended a median of seven classes; additionally, seven of the yoga participants (54%) reported continuing yoga at home during the follow-up period. No serious adverse events were related to the study. Secondary outcomes showed no group effects of yoga compared with usual care. CONCLUSIONS: A relaxation-based yoga programme was found to be feasible and safe for participants with rheumatoid arthritis-related pain and functional disability. Adverse events were minor, and not unexpected from an intervention including physical components. This pilot provides a framework for larger intervention studies, and supports further exploration of yoga as a complex intervention to assist with the management of rheumatoid arthritis.
28850027 MiR-338-5p suppresses rheumatoid arthritis synovial fibroblast proliferation and invasion 2018 Mar OBJECTIVES: We proposed to find out the role of miR-338-5p played in cell proliferation and invasion of rheumatoid arthritis synovial fibroblasts (RASFs) by regulating ADAMTS-9. METHODS: QRT-PCR was performed to quantify the miR-338-5p and ADAMTS-9 mRNA expression in RA sample tissues and normal synovial tissues. Western blot was performed to evaluate the ADAMTS-9 protein levels in transfected RASFs. Luciferase reporter assays were used to demonstrate whether miR338-5p directly targets ADAMTS-9. MTT, Transwell and wound healing assays were respectively used to evaluate the growth and mobility of RASFs. Flow cytometry was applied to detect cell cycle distributions and apoptosis rates in transfected RASFs. RESULTS: MiR-338-5p was significantly downregulated in rheumatoid arthritis (RA) tissues while ADAMTS-9 was obviously overexpressed (p<0.001). Luciferase reporter assays demonstrated that miR-338-5p directly targeted ADAMTS-9. Moreover, overexpression of miR-338-5p suppressed RASFs biological functions and induced G0/G1 arrest and apoptosis of RASFs (p<0.001), while all the effects could be efficiently attenuated by the upregulation of ADAMTS-9. CONCLUSIONS: By inhibiting ADAMTS-9, miR-338-5p suppressed the proliferation and metastasis of rheumatoid arthritis synovial fibroblasts. Thus, replenishing miR-338-5p may be a potential therapy for the clinic management of RA.
27341562 Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells i 2017 Jan 1 BACKGROUND: Dipeptidyl peptidase IV (DPPIV/CD26) plays an important role in T cell activation and immune regulation, however the role of this enzyme in early rheumatoid arthritis (eRA) has not been clearly defined. The aim of this study was to determine the serum activity of DPPIV, its expression on peripheral blood mononuclear cells (PBMC) and to examine possible correlations with disease activity (DAS28) in untreated patients with eRA. METHODS: The study included 50 patients newly diagnosed with RA, who had not received any corticosteroid or disease modifying antirheumatic drugs (DMARD) therapy and whose conventional radiographs of hands and feet showed no structural damage. The control group consisted of 40 healthy volunteers. Also, 30 patients with chronic RA (cRA) were examined. The serum activity of DPPIV was determined by the direct photometric method, while expression of CD26 on PBMC was determined using flow cytometry. RESULTS: Decreased DPPIV serum activity was detected in patients with eRA and cRA compared to the control group (p=0.024, p<0.0001, respectively). Although, the percentage of overall CD26+ white blood cells (WBC) was significantly decreased in eRA patients (p<0.001), the percentage of CD26+ lymphocytes and monocytes and mean fluorescence intensity of CD26 on these cells in eRA patients showed no significant difference compared to healthy volunteers. DAS28 showed no significant correlation with CD26 expression or DPPIV serum activity, but a significant inverse correlation between the duration of symptoms and DPPIV serum activity was observed. CONCLUSIONS: Our results show that a decrease in DPPIV serum activity, but not CD26 expression, is present in an early stage of rheumatoid arthritis.
28627096 High titer of anti-citrullinated peptide antibody is a risk factor for severe carotid athe 2017 Aug AIM: Cardiovascular disease is one of the complications of rheumatoid arthritis (RA). We researched the morbidity and severity of existing carotid atherosclerosis plaque and associated risk factors in patients with RA. METHOD: This study included 413 participants, including 208 patients with RA and 205 age- and sex-matched healthy volunteers. Carotid ultrasound, clinical data collection and assessment of cardiovascular risk factors were performed. Atherosclerotic plaque was defined as an intima-media thickness ≥ 1.1 mm. Severity of plaque was assessed by plaque score, defined as the sum of the maximal thickness of all plaques in bilateral carotid arteries. RESULTS: Data were analyzed from 200 patients with RA and 202 controls. Carotid plaque was observed more frequently in patients with RA than controls (47.0 vs. 36.1%, P = 0.027). Moreover, plaque score was significantly higher in RA patients (P = 0.032). In logistic regression analysis, RA represented an independent risk factor for the presence of plaque (adjusted odds ratio, 1.68; 95% confidence interval, 1.03-2.74). Comparing RA patients with and without plaque, anti-cyclic citrullinated peptide (anti-CCP) antibodies titer was significantly higher in patients with plaque (315.8 ± 454.1 U/mL) than in patients without (165.7 ± 281.1 U/mL; P = 0.005). Moreover, multiple linear regression analysis clarified that anti-CCP antibody titer was associated with plaque score in patients with RA. CONCLUSION: High prevalence of any carotid plaques and severe carotid plaques were more frequent in patients with RA. High titer of anti-CCP antibodies represented a risk factor for severe carotid atherosclerotic plaque in patients with RA.
28506320 Costs associated with failure to respond to treatment among patients with rheumatoid arthr 2017 May 15 BACKGROUND: Tumor necrosis factor inhibitors (TNFi) are common second-line treatments for rheumatoid arthritis (RA). This study was designed to compare the real-world clinical and economic outcomes between patients with RA who responded to TNFi therapy and those who did not. METHODS: For this retrospective cohort analysis we used medical and pharmacy claims from members of 14 large U.S. commercial health plans represented in the HealthCore Integrated Research Database. Adult patients (aged ≥18 years) diagnosed with RA and initiating TNFi therapy (index date) between 1 January 2007 and 30 April 2014 were included in the study. Treatment response was assessed using a previously developed and validated claims-based algorithm. Patients classified as treatment responders in the 12 months postindex were matched 1:1 to nonresponders on important baseline characteristics, including sex, age, index TNFi agent, and comorbidities. The matched cohorts were then compared on their all-cause and RA-related healthcare resource use, and costs were assessed from a payer perspective during the first, second, and third years postindex using parametric tests, regressions, and a nonparametric bootstrap. RESULTS: A total of 7797 patients met the study inclusion criteria, among whom 2337 (30%) were classified as treatment responders. The responders had significantly lower all-cause hospitalizations, emergency department visits, and physical/occupational therapy visits than matched nonresponders during the first-year postindex. Mean total all-cause medical costs were $5737 higher for matched nonresponders, largely driven by outpatient visits and hospitalizations. Mean all-cause pharmacy costs (excluding costs of biologics) were $354 higher for matched nonresponders. Mean RA-related pharmacy costs (conventional synthetic and biologic drugs), however, were $8579 higher in the responder cohort, driven by higher adherence to their index TNFi agent (p < 0.01 for all comparisons). A similar pattern of cost differentiation was observed over years 2 and 3 of follow-up. CONCLUSIONS: In this real-world study we found that, compared with matched nonresponders, patients who responded to TNFi treatments had lower all-cause medical, pharmacy, and total costs (excluding biologics) up to 3 years from initiation of TNFi therapy. These cost differences between the two cohorts provide a considerable offset to the cost of RA medications and should encourage close monitoring of treatment response to minimize disease progression with appropriate therapy choices.
29205926 A retrospective review of the persistence on bDMARDs prescribed for the treatment of rheum 2018 Aug AIM: To describe the persistence of biologic disease modifying anti-rheumatic drugs (bDMARDs) in Australian rheumatoid arthritis (RA) patients, and assess the influence of methotrexate and other conventional DMARD (cDMARD) concomitant medications, and treatment line on bDMARD persistence and glucocorticoids usage. METHOD: RA patients, from the 10% Australian Medicare random sample, aged ≥18 for whom bDMARDs were dispensed were included. Individual sub-cutaneous (SC) anti-tumor necrosis factor-α (anti-TNFα) agents were combined as they were equivalent. RESULTS: Data from 1230 patients were analyzed. For all patients the 12-month persistence rates (based on Kaplan-Meier estimates) were 76% for intravenous (IV) tocilizumab, 63% abatacept (SC/IV), 61% SC-anti-TNFs and 36% IV-infliximab. Persistence rates on first-line bDMARDs were 79% (tocilizumab and abatacept), 64% (SC-anti-TNFs) and 13% (infliximab); rates were sustained for tocilizumab but dropped to 49% for abatacept and 51% for SC-anti-TNFs in the second-line setting. Median treatment persistence was 40 months tocilizumab (95% CI: 30-ND), 33 months abatacept (95% CI: 20-ND); 22 months SC-anti-TNF (95% Cl: 18-27), and 4 months infliximab (95% CI: 2-13). Longer persistence was observed for SC-anti-TNFs and abatacept combined with methotrexate or other cDMARDs. For tocilizumab, persistence was robust with or without concomitant medications. The median oral glucocorticoid doses decreased from 4.1 mg/day (min 0, max 21) to 2.0 mg/day (min 0, max 17.3) over 2 years. CONCLUSIONS: Treatment persistence was longer on tocilizumab followed by abatacept then SC-anti-TNF therapy and was influenced by co-therapy. Glucocorticoid dosage decreased with bDMARD use. This real-world data highlights that persistence on bDMARDs differs according to biologics mode of action and co-therapy.
27974851 Mechanisms leading from systemic autoimmunity to joint-specific disease in rheumatoid arth 2017 Feb A key unanswered question in the pathophysiology of rheumatoid arthritis (RA) is how systemic autoimmunity progresses to joint-specific inflammation. In patients with seropositive RA (that is, characterized by the presence of autoantibodies) evidence is accumulating that immunity against post-translationally modified (such as citrullinated) autoantigens might be triggered in mucosal organs, such as the lung, long before the first signs of inflammation are seen in the joints. However, the mechanism by which systemic autoimmunity specifically homes to the joint and bone compartment, thereby triggering inflammation, remains elusive. This Review summarizes potential pathways involved in this joint-homing mechanism, focusing particularly on osteoclasts as the primary targets of anti-citrullinated protein antibodies (ACPAs) in the bone and joint compartment. Osteoclasts are dependent on citrullinating enzymes for their normal differentiation and are unique in displaying citrullinated antigens on their cell surface in a non-inflamed state. The binding of ACPAs to osteoclasts releases the chemokine IL-8, leading to bone erosion and pain. This process initiates a chain of events that could lead to attraction and activation of neutrophils, resulting in a complex series of proinflammatory processes in the synovium, eventually leading to RA.
28677621 Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with R 2017 Jul 4 Genes involved in regulation of the nuclear factor-κB (NF-κB)-pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of TLR2, TLR4, TLR9 and NF-κB1 genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-α therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for TLR2 (rs111200466), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and NF-κB1 (rs28362491) alleles. The presence of the TLR9 -1486 T variant (p < 0.0001) and its homozygosity (p < 0.0001) were found to be associated with disease susceptibility. The TLR9 -1237 C allele was associated with predisposition to RA in females only (p = 0.005). Moreover, the TLR4 rs4986791 G (rs4986790 T) alleles were more frequently detected among patients with the stage IV disease (p = 0.045), and were associated with more effective response to anti-TNF-α therapy (p = 0.012). More efficient response to anti-TNF-α treatment was also observed in patients with del within the NF-κB1 gene (p = 0.047), while for the TLR9 -1486 T homozygotes, the treatment was ineffective (p = 0.018). TLR polymorphisms affect disease susceptibility and response to therapy with TNF-α inhibitors in RA patients of Caucasian origin.
28552525 Upregulated KAT7 in synovial fibroblasts promotes Th17 cell differentiation and infiltrat 2017 Jul 22 Rheumatoid arthritis (RA) is a chronic autoimmune disease involving multiple cellular participants, of which synovial fibroblasts (SFs) are tightly connected with the development and progression of RA. Here, we provide evidence confirming that KAT7, an H4-specific histone acetylase, is upregulated in SFs of RA patients, which is at least attributed to the stimulation by RA-associated proinflammatory cytokines, such as TNF-α, IL-1β or IFN-γ. In addition, KAT7 overexpression in cultured human fibroblast-like synoviocytes (HFLSs) induces IL-6 and TGF-β expression through an epigenetic mechanism, and in vitro T helper 17 (Th17) cell polarization cultured in these supernatants shows promoted cell differentiation. Moreover, KAT7 overexpression in HFLSs induces CCL20 expression via p44/42 MAPK pathway, whereby promoting Th17 cell migration. These two activities of KAT7 in RA SFs indicate its potential roles in accelerating RA pathology. Overall, these results demonstrate some connections between KAT7 upregulated in RA SFs and RA progression and present the inhibition of KAT7 activity as a novel therapeutic target for interfering RA disease.
28262590 The implications of biologic therapy for elective foot and ankle surgery in patients with 2017 Mar INTRODUCTION: Rheumatoid arthritis (RA) is one of a number of inflammatory arthropathies resulting in foot pain and deformity. Patients with this disease may require surgical intervention as part of their management. Many of these patients are now taking biologic agents which pose several risks to patients in the perioperative phase. The surgical team therefore need to be aware of these associated complications and how to manage these cases. AIM: This paper aims to review the current literature about perioperative needs (foot and ankle surgery) associated with patients with rheumatoid arthritis receiving biologic therapy. MAIN FINDINGS: The majority of the literature discusses the perioperative complications associated with patients on anti-TNFα therapy with few studies investigating the other biologics in common use. There is conflicting evidence as to the safety of continuing or stopping biologic drug therapy prior to orthopaedic procedures. The British Society for Rheumatology (BSR) have produced guidelines for the management of patients on anti-TNFα therapy or the biologic agent Tocilizumab. These recommendations suggest the risks of post-operative infection need to be balanced against the risk of a post-operative disease flare. In essence, it is suggested anti-TNFα therapy is stopped 3-5 times the half-life of the drug whilst Tocilizumab is stopped 4 weeks prior to surgery. CONCLUSION: Good communication is needed between the surgical team and the local Rheumatology department managing the patient's disease in order to optimise perioperative care. Local pathways may vary from the BSR recommendations to determine the most suitable course of action with regards to continuing or stopping biologic therapy prior to foot and ankle surgery.
28293635 Semiquantitative Evaluation of Extrasynovial Soft Tissue Inflammation in the Shoulders of 2017 Objectives. To develop a scoring system for evaluating the extrasynovial soft tissue inflammation of the shoulders in patients with polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis with PMR-like onset (pm-EORA) using ultrasound. Methods. We analyzed stored power Doppler (PD) images obtained by the pretreatment examination of 15 PMR patients and 15 pm-EORA patients. A semiquantitative scoring system for evaluating the severity of PD signals adjacent to the anterior aspect of the subscapularis tendon was designed. Results. A four-point scale scoring for the hyperemia on the subscapularis tendon was proposed as follows in brief: 0 = absent or minimal flow, 1 = single vessel dots or short linear-shape signals, 2 = long linear-shape signals or short zone-shape signals, or 3 = long zone-shape signals. This scoring system showed good intra- and interobserver reliability and good correlation to quantitative pixel-counting evaluation. By using it, we demonstrated that inflammation in PMR is dominantly localized in extrasynovial soft tissue as compared with pm-EORA. Conclusions. We proposed a reliable semiquantitative scoring system using ultrasound for the evaluation of extrasynovial soft tissue inflammation of the shoulders in patients with both PMR and pm-EORA. This system is simple to use and can be utilized in future investigations.
27991858 EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. 2017 Mar BACKGROUND: During the transition to rheumatoid arthritis (RA) many patients pass through a phase characterised by the presence of symptoms without clinically apparent synovitis. These symptoms are not well-characterised. This taskforce aimed to define the clinical characteristics of patients with arthralgia who are considered at risk for RA by experts based on their clinical experience. METHODS: The taskforce consisted of 18 rheumatologists, 1 methodologist, 2 patients, 3 health professionals and 1 research fellow. The process had three phases. In phase I, a list of parameters considered characteristic for clinically suspect arthralgia (CSA) was derived; the most important parameters were selected by a three-phased Delphi approach. In phase II, the experts evaluated 50 existing patients on paper, classified them as CSA/no-CSA and indicated their level of confidence. A provisional set of parameters was derived. This was studied for validation in phase III, where all rheumatologists collected patients with and without CSA from their outpatient clinics. RESULTS: The comprehensive list consisted of 55 parameters, of which 16 were considered most important. A multivariable model based on the data from phase II identified seven relevant parameters: symptom duration <1 year, symptoms of metacarpophalangeal (MCP) joints, morning stiffness duration ≥60 min, most severe symptoms in early morning, first-degree relative with RA, difficulty with making a fist and positive squeeze test of MCP joints. In phase III, the combination of these parameters was accurate in identifying patients with arthralgia who were considered at risk of developing RA (area under the receiver operating characteristic curve 0.92, 95% CI 0.87 to 0.96). Test characteristics for different cut-off points were determined. CONCLUSIONS: A set of clinical characteristics for patients with arthralgia who are at risk of progression to RA was established.
27456070 PPARγ agonist rosiglitazone inhibits migration and invasion by downregulating Cyr61 in rh 2017 Oct AIM: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have anti-inflammatory properties that reduce inflammatory cytokine production in rheumatoid arthritis (RA). Cysteine-rich angiogenic inducer 61 (Cyr61) is associated with diseases related to chronic inflammation. The aim of this study was to investigate the mechanisms underlying the effects of PPARγ agonists on tumor necrosis factor (TNF)-α-induced fibroblast-like synoviocyte (FLS) invasion and migration, as well as Cyr61 production, in RA-FLS. METHODS: FLS were cultured with TNF-α and Cyr61 in the presence or absence of PPARγ agonists. Matrix metalloproteinase and Cyr61 expression levels in RA-FLS and culture supernatants were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The migration and invasion phenotypes of RA-FLS were determined by wound healing and Boyden chamber assays. RESULTS: Cyr61 protein was expressed in RA-FLS, and its intracellular expression and secretion levels were increased by TNF-α. Moreover, Cyr61 directly promoted RA-FLS migration and invasion. Rosiglitazone (RSG) significantly decreased TNF-α-induced Cyr61 expression. RSG decreased TNF-α-induced nuclear factor (NF)-κB activation and inhibitor of κBα degradation. Furthermore, RSG inhibited TNF-α-induced RA-FLS migration and invasion and decreased Cyr61 treatment-induced RA-FLS invasion. Finally, blocking Cyr61 significantly attenuated TNF-α-induced migration. CONCLUSIONS: Our results demonstrate for the first time that PPARγ agonists may have beneficial effects on the migration and invasion of RA-FLS via the downregulation of Cyr61. Therefore, PPARγ agonists could be potential treatment targets for RA.
28547208 Pulse wave velocity and augmentation index are not independently associated with carotid a 2017 Nov Arterial stiffness can enhance cardiovascular risk by increasing atherogenesis or adverse hemodynamic effects. We examined whether the arterial stiffness markers of aortic pulse wave velocity (PWV) and the augmentation index (AIx) are independently associated with carotid artery intima-media thickness (IMT) and plaque in patients with rheumatoid arthritis (RA). PWV and AIx were determined by brachial oscillometry using the Mobil-O-Graph® system and carotid IMT and plaque by ultrasound in 194 consecutive RA patients without established cardiovascular disease, chronic kidney disease, and diabetes at disease onset. In crude analysis, PWV was associated with IMT (β (95% CI) = 0.04 (0.03 to 0.05), p value < 0.0001) and plaque (OR (95% CI) = 1.69 (1.40 to 2.04), p value < 0.0001). Upon adjustment for the confounders of age, sex, mean blood pressure, body height, and cardiovascular risk factors comprising smoking, the atherogenic index, and diabetes, PWV was not related to IMT (β (95% CI) = 0.01 (-0.02 to 0.04), p value = 0.5) or plaque (OR (95% CI) = 0.99 (0.96 to 1.01), p value = 0.3). AIx was not associated with IMT in crude (β (95% CI) = -0.002 (-0.004 to 0.007), p value = 0.2) and adjusted analyses (β (95% CI) = -0.002 (-0.004 to 0.000), p value = 0.06). AIx was also unrelated to carotid plaque in crude (OR (95% CI) = 1.04 (0.60 to 1.82), p value = 0.9) and adjusted analyses (OR (95% CI) = 0.97 (0.94 to 1.01), p value = 0.1). PWV and AIx are not independently associated with subclinical carotid atherosclerosis in RA.
29199605 Modeling Mesenchymal Stem Cells in TMJ Rheumatoid Arthritis and Osteoarthritis Therapy. 2017 Stem cells have self-renewal capacity and an ability to differentiate into particular cell types generating mature cells. Mesenchymal stem cells (MSCs) have a significant role in tissue homeostasis, which leads into tissue regeneration. MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs are also believed to have therapeutic power over temporomandibular joint (TMJ) disorders (TMDs). The most common type of TMD is articular disc displacement, which induces progressive degenerative changes. These changes lead to rheumatoid arthritis or osteoarthritis. In this review, use of human mesenchymal cells (hMSCs) for therapeutic treatment of inflammatory diseases of TMJ is discussed.
28553958 Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis. 2017 Jul Recent evidence suggests that a substantial portion of complex disease risk alleles modify gene expression in a cell-specific manner. To identify candidate causal genes and biological pathways of immune-related complex diseases, we conducted expression quantitative trait loci (eQTL) analysis on five subsets of immune cells (CD4(+) T cells, CD8(+) T cells, B cells, natural killer (NK) cells and monocytes) and unfractionated peripheral blood from 105 healthy Japanese volunteers. We developed a three-step analytical pipeline comprising (i) prediction of individual gene expression using our eQTL database and public epigenomic data, (ii) gene-level association analysis and (iii) prediction of cell-specific pathway activity by integrating the direction of eQTL effects. By applying this pipeline to rheumatoid arthritis data sets, we identified candidate causal genes and a cytokine pathway (upregulation of tumor necrosis factor (TNF) in CD4(+) T cells). Our approach is an efficient way to characterize the polygenic contributions and potential biological mechanisms of complex diseases.
28032846 Non-adherence to subcutaneous biological medication in patients with rheumatoid arthritis: 2017 May OBJECTIVES: To evaluate non-adherence to prescribed subcutaneous biologicals in rheumatoid arthritis (RA) patients in Spain. METHODS: ARCO (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs) was a multicentre, non-interventional retrospective study involving 42 rheumatology clinics from representative hospitals throughout Spain. The primary objective was to assess the percentage of patients (aged ≥18 years with an established RA diagnosis) with non-adherence to prescribed subcutaneous biologicals using clinical records and hospital pharmacy dispensing logs as the primary information sources. Adherence was assessed using the Medication Possession Ratio (MPR). Additionally, patients completed the Morisky-Green Medication Adherence Questionnaire. RESULTS: A total of 364 patients (77.5% females, mean age 54.9 years, median RA duration since diagnosis 7.8 years) were enrolled in ARCO. Non-adherence (MPR ≤80%) was reported in 52/363 evaluable patients (14.3%), and was lower in patients receiving initial monthly drug administration (6.4%) than with weekly (17.4%; p=0.034) or every two weeks (14.4%; p=0.102) administration. By multivariate analysis, non-adherence was positively associated with RA duration above the median and with using induction doses. Monthly administration, compared to weekly administration, was inversely associated with non-adherence. Age, gender, order of administration, and changes in the interval of administration, showed no association with non-adherence. Compared with the MPR, the Morisky-Green questionnaire performed poorly in detecting non-adherence. CONCLUSIONS: Non-adherence to the prescribed subcutaneous biological drug occurred in 14.3% of patients with RA. Patients using the most convenient administration period (i.e. monthly) had better adherence than those using more frequent dosing schedules.
27844125 Increased risk of rheumatoid arthritis in patients with migraine: a population-based, prop 2017 Feb Previous cross-sectional studies have suggested an association between migraine and rheumatoid arthritis (RA), but no longitudinal study has been performed to evaluate the temporal relationship between the two conditions. The purpose of the present population-based, propensity score-matched cohort study was to investigate whether migraineurs are at a higher risk of developing RA. A total of 58,749 subjects aged between 20 and 90 years with at least two ambulatory visits with a diagnosis of migraine were recruited in the migraine group. We fit a logistic regression model that included age, sex, comorbid conditions, and socioeconomic status as covariates to compute the propensity score. The non-migraine group consisted of 58,749 propensity score-matched, randomly sampled subjects without migraine. The RA-free survival curves were generated using the Kaplan-Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of RA. During follow-up, 461 subjects in the migraine group and 220 in the non-migraine group developed RA. The incidence rate of RA was 3.18 (95% confidence interval [CI] 2.90-3.49) per 1000 person-years in the migraine group and 1.54 (95% CI 1.34-1.76) per 1000 person-years in the non-migraine group. Compared to the non-migraine group, the crude hazard ratio of RA for the migraine group was 2.15 (95% CI 1.82-2.56, P < 0.0001), and the multivariable-adjusted hazard ratio was 1.91 (95% CI 1.58-2.31, P < 0.0001). This study showed that patients with migraine had an increased risk of developing RA.
28704431 Modulation of platelet-derived microparticles to adhesion and motility of human rheumatoid 2017 Platelet-derived microparticles (PMPs) are closely associated with disease activity in rheumatoid arthritis (RA) and contribute to the inflammatory process. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) play important roles in the progression of joint destruction. The aim of this study is to demonstrate whether PMPs affect the adhesion and motility of RA-FLSs. Our data indicated that PMPs promoted migration, invasion and adhesion to extracellular matrix (ECM) of RA-FLSs. Further study showed that PMPs up-regulated the expression of matrix metalloproteinase-1 (MMP1) and increased the level of phosphorylation of NF-κB (p-NF-κB) and Erk (p-Erk) in RA-FLSs. These results suggest that PMPs promote RA-FLSs adhesion and motility presumably by increasing MMP1 via activating Erk-mediated NF-κB pathway.