Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
26635805 High-Risk Cardiovascular Patients: Clinical Features, Comorbidities, and Interconnecting M 2015 Cardiovascular disease is the leading cause of death in the Western world with an increase over the last few decades. Atherosclerosis with its different manifestations in the coronary artery tree, the cerebral, as well as peripheral arteries is the basis for cardiovascular events, such as myocardial infarction, stroke, and cardiovascular death. The pathophysiological understanding of the mechanisms that promote the development of vascular disease has changed over the last few decades, leading to the recognition that inflammation and inflammatory processes in the vessel wall are major contributors in atherogenesis. In addition, a subclinical inflammatory status, e.g., in patients with diabetes or the presence of a chronic inflammatory disease, such as rheumatoid arthritis, have been recognized as strong risk factors for cardiovascular disease. The present review will summarize the different inflammatory processes in the vessel wall leading to atherosclerosis and highlight the role of inflammation in diabetes and chronic inflammatory diseases for cardiovascular morbidity and mortality.
26450275 [Orthopedic shoes: Still in touch with the times?]. 2015 Nov BACKGROUND: Deformities of the foot due to rheumatic disease, particularly rheumatoid arthritis, occur in 85-95% of patients during the course of their disease. OBJECTIVE: This study investigates whether treatment with orthopedic shoes still has a place in modern therapies. RESULTS: Foot orthotics and technical orthopedic shoes can play an important role in purely conservative treatment as well as postoperative therapy. CONCLUSION: Due to a lack of knowledge concerning modern orthopedic shoe techniques, this treatment option has slipped out of focus--in part because of its association with the old-fashioned unshapely black orthopedic shoes. Nevertheless, these shoes can contribute significantly to maintenance of patient mobility; a factor of extreme importance to the individuals who already suffer considerably from the disease per se.
26261542 Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibr 2015 Activated synovial fibroblasts in rheumatoid arthritis (RASF) play a critical role in the pathology of rheumatoid arthritis (RA). Recent studies suggested that deregulation of microRNAs (miRs) affects the development and progression of RA. Therefore, we aimed to identify de-regulated miRs in RASF and to identify target genes that may contribute to the aggressive phenotype of RASF. Quantitative real-time PCR revealed a marked downregulation of miR-188-5p in synovial tissue samples of RA patients as well as in RASF. Exposure to the cytokine interleukine-1β lead to a further downregulation of miR-188-5p expression levels compared to control cells. Re-expression of miR-188-5p in RASF by transient transfection significantly inhibited cell migration. However, miR-188-5p re-expression had no effects on glycosaminoglycan degradation or expression of repellent factors, which have been previously shown to affect the invasive behavior of RASF. In search for target genes of miR-188-5p in RASF we performed gene expression profiling in RASF and found a strong regulatory effect of miR-188-5p on the hyaluronan binding protein KIAA1199 as well as collagens COL1A1 and COL12A1, which was confirmed by qRT-PCR. In silico analysis revealed that KIAA1199 carries a 3'UTR binding site for miR-188-5p. COL1A1 and COL12A1 showed no binding site in the mRNA region, suggesting an indirect regulation of these two genes by miR-188-5p. In summary, our study showed that miR-188-5p is down-regulated in RA in vitro and in vivo, most likely triggered by an inflammatory environment. MiR-188-5p expression is correlated to the activation state of RASF and inhibits migration of these cells. Furthermore, miR-188-5p is directly and indirectly regulating the expression of genes, which may play a role in extracellular matrix formation and destruction in RA. Herewith, this study identified potential novel therapeutic targets to inhibit the development and progression of RA.
26251654 A proteomic profile of synoviocyte lesions microdissected from formalin-fixed paraffin-emb 2015 BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovial joints. Early intervention followed by early diagnosis can result in disease remission; however, both early stage diagnosis and provision of effective treatment have been impeded by the heterogeneity of RA, which details of pathological mechanism are unclear. Regardless of numerous investigations of RA by means of genomic and proteomic approaches, proteins interplaying in RA synovial tissues that contain various types of synoviocytes, are not yet sufficiently understood. Hence we have conducted an HPLC/mass spectrometry-based exploratory proteomic analysis focusing on synoviocyte lesions laser-microdissected (LMD) from formalin-fixed paraffin-embedded (FFPE) synovial tissues (RA, n = 15; OA, n = 5), where those of Osteoarthritis (OA) were used as the control. RESULTS: A total of 508 proteins were identified from the RA and OA groups. With the semi-quantitative comparisons, the spectral index (SpI), log2 protein ratio (R SC ) based on spectral counting, and statistical G-test, 98 proteins were found to be significant (pair-wise p < 0.05) to the RA synovial tissues. These include stromelysin-1 (MMP3), proteins S100-A8 and S100-A9, plastin-2, galectin-3, calreticulin, cathepsin Z, HLA-A, HLA-DRB1, ferritin, neutrophil defensin 1, CD14, MMP9 etc. CONCLUSIONS: Our results confirmed the involvement of known RA biomarkers such as stromelysin-1 (MMP3) and proteins S100-A8 and S100-A9, and also that of leukocyte antigens such as HLA-DRB1. Network analyses of protein-protein interaction for those proteins significant to RA revealed a dominant participation of ribosome pathway (p = 5.91 × 10(-45)), and, interestingly, the associations of the p53 signaling (p = 2.34 × 10(-5)). An involvement of proteins including CD14, S100-A8/S100-A9 seems to suggest an activation of the NF-kB/MAPK signaling pathway. Our strategy of laser-microdissected FFPE-tissue proteomic analysis in Rheumatoid Arthritis thus demonstrated its technical feasibility in profiling proteins expressed in synovial tissues, which may play important roles in the RA pathogenesis.
27536202 Association of the polymorphisms of TRAF1 (rs10818488) and TNFAIP3 (rs2230926) with rheuma 2016 AIM OF THE STUDY: Recent studies demonstrated the association of tumor necrosis factor α-induced protein 3 (TNFAIP3) (rs2230926) and tumor necrosis factor receptor associated factor 1 (TRAF1) (rs10818488) with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in different populations. We aimed at determining whether they confer susceptibility to SLE and RA in Egyptian population and if there is any relation to disease activity and auto-antibodies profile. MATERIAL AND METHODS: A case-control study involving 105 individuals with RA, 90 with SLE and 75 healthy controls was performed using TaqMan genotyping assay for two SNPs that showed the best evidence of association in the previous Caucasian studies. RESULTS: We detected significant differences in G allele frequency of TNFAIP3 (rs2230926) with SLE (p = 0.017(*)) and RA (OR = 2.333; 95% CI: 1.103-4.935, p = 0.023(*)) and association with RA disease activity (< 0.001). The A allele of TRAF1 was significantly increased in RA compared to controls(p = 0.049) and with RA activity (p = 0.001), while TRAF1 polymorphism did not exhibit any significant difference in the frequencies of genotypes or alleles in SLE and control (p = 0.280). CONCLUSIONS: TNFAIP3 is a susceptibility gene to SLE and RA in the Egyptian population and is correlated to disease activity and the presence of autoantibodies while TRAF1 polymorphisms increase the risk of RA but not to SLE in Egyptian populations.
27073419 Management of rheumatoid arthritis: Impact and risks of various therapeutic approaches. 2016 Apr Rheumatic diseases are highly prevalent chronic disorders and the leading cause of physical disability worldwide, with a marked socio-economic impact. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown etiology with an autoimmune pathogenesis, characterised by arthropathy with chronic, deforming, destructive evolution and multiple systemic manifestations. The management of RA has undergone significant changes as far as objectives and approaches are concerned, ending in the current strategy known as 'treat to target'. The therapeutic array of RA includes several categories of medicinal products, of varying potential. There are several criteria for the classification of medicinal products used against this disease, one of the most important and modern of which divides such substances according to their effects on the progress of the disease: symptom-modifying antirheumatic drugs (including non-steroidal anti-inflammatory drugs and corticoids), disease-modifying antirheumatic drugs (including various substances, such as gold salts, antimalarials, sulfasalazine, D-penicillamine; non-specific immunosuppressive medication, such as methotrexate, cyclophosphamide, azathioprine and leflunomide) and biological therapy is a recent addition, providing new insight into the treatment of this disease. The selection of the optimal therapy for RA should be based on guidelines and recommendations, but also on clinical particular aspects and patient preferences.
26819749 Regulation of peripheral classical and non-classical monocytes on infliximab treatment in 2016 OBJECTIVE: To investigate the regulatory effect of tumour necrosis factor (TNF) blockade with infliximab on the distribution of peripheral blood monocyte subpopulations in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Purified CD11b+CD14+ monocytes from 5 patients with RA and 5 AS were analysed ex vivo before and after infliximab treatment by flow cytometry for CD16, CD163, CD11b, C-C chemokine receptor type 2 (CCR2) and CXC chemokine receptor 4 (CXCR4) at baseline and at days 2, 14, 84 and 168 after the first infliximab administration. Serum levels of the stromal cell-derived factor (SDF)-1 and monocyte chemotactic peptide (MCP)-1 at different time points were measured in either patient group before and on infliximab treatment. RESULTS: Anti-TNF treatment with infliximab led to a significant increase of circulating CD11b+ non-classical and a concomitantly decrease of CD11b+ classical monocytes, to a decline in SDF-1 levels and reduced expression of CCR2 and CXCR4 on non-classical monocyte subpopulation. CONCLUSIONS: Our study shows, that TNFα blockade by infliximab resulted in a dichotomy of the regulation of classical and non-classical monocytes that might have substantial impact on inhibition of osteoclastogenesis and of subsequent juxta-articular bone destruction and systemic bone loss in RA and AS.
29698201 How Quality of Life as Patient-Reported Outcome Has Been Studied for Rheumatoid Arthritis 2015 May OBJECTIVE: To review the use of health-related quality-of-life (HRQOL) instruments as patient-reported outcome in patients with rheumatoid arthritis (RA) in studies that have been published in Chinese-speaking populations. METHODS: Overlapping searching strategy was used using four publication databases: PubMed and EMBASE for English publications and Wanfang and CNKI for Chinese publications. Entries published between January 1, 1990, and July 31, 2014, were retrieved and then reviewed independently by two researchers. The identified studies were summarized according to information source, publishing year, study location, and study type. The validation studies were examined closely in terms of their sample sizes and psychometric properties. RESULTS: There were 99 studies from the databases selected for review. Among the studies reviewed, most studies were conducted in Mainland China. There was a clear overall increasing trend in the number of studies in recent years. Generic instruments were more frequently used by researchers outside China. Another observation was that most instruments were used without previous validation either in any Chinese-speaking population with RA or in the specific country that it was used. CONCLUSIONS: The importance of patient-reported quality of life as an outcome indicator in patients with RA is more and more realized in Chinese-speaking regions during the past two decades. To facilitate the use of HRQOL for better management of patients, and improve the quality of research, there is a strong need of validating the HRQOL instruments in more locations with a larger population, more comprehensive validity, and potential cross-cultural validation in future.
25642219 Interaction between extracellular matrix molecules and microbial pathogens: evidence for t 2014 Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation followed by tissue rebuilding or fibrosis. A failure by the body to regulate inflammation effectively is one of the hallmarks of RA. The interaction between the external environment and the human host plays an important role in the development of autoimmunity. In RA, the observation of anti-cyclic citrullinated peptide antibodies (ACPA) to autoantigens is well recognized. Citrullination is a post-translational modification mediated by peptidyl arginine deiminases, which exist in both mammalian and bacterial forms. Previous studies have shown how proteins expressed in the human extracellular matrix (ECM) acquire properties of damage-associated molecular patterns (DAMPs) in RA and include collagens, tenascin-C, and fibronectin (FN). ECM DAMPs can further potentiate tissue damage in RA. Recent work has shown that citrullination in RA occurs at mucosal sites, including the oral cavity and lung. Mucosal sites have been linked with bacterial infection, e.g., periodontal disease, where exogenous pathogens are implicated in the development of autoimmunity via an infectious trigger. Proteases produced at mucosal sites, both by bacteria and the human host, can induce the release of ECM DAMPs, thereby revealing neoepitopes which can be citrullinated and lead to an autoantibody response with further production of ACPA. In this perspectives article, the evidence for the interplay between the ECM and bacteria at human mucosal surfaces, which can become a focus for citrullination and the development of autoimmunity, is explored. Specific examples, with reference to collagen, fibrinogen, and FN, are discussed.
27830032 Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxid 2016 Rheumatoid arthritis (RA) is a chronic inflammatory disease which results in progressive destruction of the joint. In this study, we examined if the hydrogen could inhibit inflammation in a mouse model of collagen-induced arthritis (CIA) via oxidative stress on RA-FLSs. Moreover, to identify the mechanisms of action, we evaluated the effect of hydrogen on RA-FLSs development and the expression of pro-inflammatory cytokines and signaling pathways. Based on our result, H(2) enriched medium can increase super oxide dismutase (SOD) level following H(2)O(2) treatment and decrease 8-hydroxy-2'-deoxyguanosine (8-OHdG) level. Since H(2)O(2) treatment activates MAPK, NF-κB and TGF-β1 in cells, our study suggested that H(2) could inhibit H(2)O(2) activated MAPK and NF-κB activation as well as TGF-β1 expression in treated cells. Taken together, our data suggested that H(2) can directly neutralize OH and ONOO(-) to reduce oxidative stress. Moreover, MAPK and NF-κB pathway also play roles in oxidative damage caused by H(2)O(2) in RA-FLSs. H(2) can provide protection to cells against inflammation, which may be related to inhibition of the activation of MAPK and NF-κB.
28905017 Treat-to-target therapy does not prevent excessive progression of carotid intima media thi 2016 INTRODUCTION: The aim of the study was to investigate the presence of subclinical atherosclerosis and predictors of change in carotid intima-media measures in early rheumatoid arthritis patients (eRA) as compared to chronic RA patients and patients without arthritis. MATERIAL AND METHODS: Fifty-five consecutive eRA patients were assessed at the time of diagnosis and after 1 year of therapy. Fifty-five sex- and age-matched chronic RA patients and 29 patients without inflammatory disease were used as controls. Carotid artery intima-media thickness (CIMT) and carotid plaques were measured at baseline and after follow-up. In eRA patients ultrasound assessment of hand joints was performed before and after treatment. Carotid artery intima-media thickness was assessed again after 2 years in 44 eRA patients. RESULTS: Carotid artery intima-media thickness progression after 1 year of therapy was higher in eRA patients compared to both control groups (p = 0.017) and correlated with symptoms duration (p = 0.017) and DMARD monotherapy (p = 0.015). Ultrasound progression of hand joint erosions was associated with longer symptoms duration (p = 0.006). After 2 years of observation CIMT progression was similar in all examined groups. CONCLUSIONS: We observed rapid CIMT progression during the first year of RA therapy. Longer symptoms duration and less aggressive therapy were associated with CIMT increase.
27398263 Matrix Metalloproteinase-9 Production by Immortalized Human Chondrocyte Lines. 2016 Jun We reported at the Keynote Forum of Immunology Summit-2015 that recombinant human (rh) TNF-α or rhIL-6 stimulated production of matrix metalloproteinase-9 (MMP-9) in the T/C28a2 and C-28/I2 human immortalized chondrocyte cell lines. Furthermore, we reported that tocilizumab (TCZ), a fully humanized monoclonal antibody which neutralizes IL-6-mediated signaling, inhibited the rhIL-6-mediated increase in the production of MMP-9. IL-6 is also a known activator of the JAK/STAT signaling pathway. In that regard, we evaluated the effect of rhIL-6 on total and phosphorylated Signal Transducer and Activator of Transcription by these chondrocyte lines which showed that whereas STAT3 was constitutively phosphorylated in T/C28a2 chondrocytes, rhIL-6 activated STAT3 in C-28/I2 chondrocytes. The finding that rhIL-6 increased the production of MMP-9 by human immortalized chondrocyte cell lines may have important implications with respect to the destruction of articular cartilage in rheumatoid arthritis and osteoarthritis. Thus, the markedly elevated level of IL-6 in rheumatoid arthritis and osteoarthritis sera and synovial fluid would be expected to generate significant MMP-9 to cause the degradation of articular cartilage extracellular matrix proteins. The finding that TCZ suppressed rhIL-6-mediated MMP-9 production suggests that TCZ, currently employed in the medical therapy of rheumatoid arthritis, could be considered as a drug for osteoarthritis.
27391167 John Cunningham (JC) virus genotypes in kidney transplant recipients, rheumatoid arthritis 2017 Feb In healthy individuals John Cunningham virus is latent without any clinical signs, but in the cases of the use of immunosuppressive drugs in graft recipients, autoimmune diseases and also increasing of age, that the immune system is suppressed it may cause disease in reactivation. Progressive multifocal leukoencephalopathy (PML) is the well-known disease caused by the virus. It has also been associated with nephropathy and tumorogensis. At present, based on vp1 capsid gene 7 genotypes have been detected. Genetic variations of JC virus in different geographical areas and the presence of different subtypes is a useful tool for reconstructing of the genetic information of JC virus and understanding of its evolution. The aim of this study was to investigate different genotypes of the JC virus in the urine of 100 kidney transplant recipients, 43 rheumatoid arthritis patients, and 100 healthy individuals as control group in Isfahan. DNA was extracted by phenol-chloroform method and subjected to a nested PCR using specific primer for vp1 capsid gene designed by Oligo 7 software. Fisher's exact test was used for statistical analyses. Using MEGA 6 software the sequences were aligned using Clustal W tool and phylogenetic trees were constructed by neighbor joining method. Thirty-one positive samples were sequenced. Genotypes 1, 3, and 4 of the virus were detected for the first time in Iran. For the first time genotype 3 was reported as the dominant genotype in Iran. For the first time in the world, genotype 4 was detected in rheumatoid arthritis patients. J. Med. Virol. 89:337-344, 2017. © 2016 Wiley Periodicals, Inc.
26688829 A Systematic Review of Peripheral and Central Nervous System Involvement of Rheumatoid Art 2015 Both central (CNS) and peripheral nervous system (PNS) complications are frequent and varied in connective tissue diseases. A systematic review was conducted between 1989 and 2014 in the databases Medline, Scopus, and Cochrane Library using the search terms, peripheral and central nervous complications and immunological profiles, to identify studies in specific connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome. A total of 675 references were identified, of which 118 were selected for detailed analysis and 22 were included in the final review with a total of 2338 participants. Our search focused only on studies upon connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome associated with seroimmunological data. The reported prevalence of CNS involvement ranges from 9 to 92% across the reported studies. However, the association between CNS and PNS manifestations and seroimmunological profiles remains controversial. Τo date, no laboratory test has been shown as pathognomonic neither for CNS nor for PNS involvement.
26351458 Rheumatoid Arthritis and the Cervical Spine: A Review on the Role of Surgery. 2015 Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease affecting a significant percentage of the population. The cervical spine is often affected in this disease and can present in the form of atlantoaxial instability (AAI), cranial settling (CS), or subaxial subluxation (SAS). Patients may present with symptoms and disability secondary to these entities but may also be neurologically intact. Cervical spine involvement in RA can pose a challenge to the clinician and the appropriate role of surgical intervention is controversial. The aim of this paper is to describe the pathology, pathophysiology, clinical manifestations, and diagnostic evaluation of rheumatoid arthritis in the cervical spine in order to provide a better understanding of the indications and options for surgery. Both the medical and surgical treatment options for RA have improved, so has the prognosis of the cervical spine disease. With the advent of disease modifying antirheumatic drugs (DMARDs), fewer patients are presenting with cervical spine manifestations of RA; however, those that do, now have improved surgical techniques available to them. We hope that, by reading this paper, the clinician is able to better evaluate patients with RA in the cervical spine and determine in which patients surgery is indicated.
27648118 [Immunity impact of pregnancy on the experience of the Obstetrics and Gynecology Departmen 2016 The influence of hormonal status during the autoimmune disease is clearly established, with peak prevalence during the reproductive years where the interest of our retrospective study of 32 cases of pregnant patients with autoimmune pathologies. Relapses of the disease during pregnancy are especially observed in pregnant with lupus erythematosus and Behçet's disease while in post-partum complications were observed in cases of rheumatoid arthritis, multiple sclerosis and scleroderma. The fetal complications depend on the stage and type of autoimmune disease and the association with other pathologies. Taking multi-disciplinary charge and adjustment of treatment resulted in stabilizing the autoimmune disease and improves fetal prognosis.
26395831 A scientific update on biosimilar infliximab (CT-P13) in rheumatic diseases. 2015 The development of biologic drugs has undoubtedly enhanced the spectrum of treatments available for immune-mediated inflammatory rheumatic diseases such as rheumatoid arthritis. However, despite their clear clinical benifits, use of biologics is often hindered by their high costs. The manufacture and subsequent approval of more cost-effective 'biosimilar' versions of these drugs may address this issue and improve patient access. CT-P13 (Remsima(®), Inflectra(®)), a biosimilar of infliximab (Remicade(®)), has shown comparable efficacy, safety and pharmacokinetics to its originator drug in clinical studies. The articles in this supplement present a scientific update on the development and use of biosimilars in rheumatic disorders, with specific focus on CT-P13. The information discussed highlights the predicted positive clinical and economic impact of biosimilars on the management of rheumatic diseases.
26835182 The Risk for Cardiovascular Events Associated with Hyperlipdemia among Patients with and W 2015 Dec OBJECTIVES: To determine, using data from a real-world setting, the overall and sex-specific risk of cardiovascular (CV) events in patients with rheumatoid arthritis (RA), with or without comorbid hyperlipidemia, relative to those in a non-RA cohort. METHODS: This retrospective cohort study using claims data from a US commercial health plan (2005-2011) included patients with RA and a matched non-RA cohort. Cox proportional hazards regression model determined the hazard ratio (HR) for CV events (myocardial infarction, stroke, revascularization procedures), using the presence of RA and hyperlipidemia as the independent variables, controlling for other covariates (age, sex, diabetes, and hypertension). RESULTS: The incidence of CV events per 1000 person-years was 10.19 for the RA cohort and 6.41 for the non-RA cohort (crude rate ratio [RR] =1.59). Within the RA cohort, incidence was 15.54 for patients with hyperlipidemia and 7.05 for patients without hyperlipidemia (crude RR=2.21); in the non-RA cohort, incidence was 10.55 and 3.82 for those with and without hyperlipidemia, respectively (crude RR=2.76). After controlling for covariates, the HR of CV events among RA patients was 1.68 (95% CI: 1.50, 1.87) relative to non-RA patients. After multivariable adjustment, hyperlipidemia conferred a significant risk of CV events in both RA and non-RA patients; the interaction between RA and hyperlipidemia was not significant (p=0.13). CONCLUSION: This real-world analysis demonstrates that patients with RA have an increased risk of CV events. Similar to a non-RA cohort, CV event rates were incrementally higher for those patients with hyperlipidemia. SIGNIFICANCE: Cardiovascular disease is an increasingly visible topic of concern in the rheumatoid arthritis community. However, there are only limited data that informs both the absolute and relative rates of CVD events, and the contribution of various risk factors such as hyperlipidemia, compared to non-RA populationsThe 'lipid paradox' hypothesis in RA suggests that elevated LDL cholesterol has a negligible effect on CVD risk in RA, unlikely in the general population where it is a well-accepted CVD risk factorThe incidence of CVD events in RA patients was 10/1000 patient years, a 1.6 fold greater risk compared to non-RA patientsThe contribution of hyperlipidemia to CVD risk was associated with comparable or greater absolute increases in the rate of CV events compared to non RA patients, a finding that does not support the lipid paradox.
28078022 MiR-19 suppresses fibroblast-like synoviocytes cytokine release by targeting toll like rec 2016 Fibroblast-like synoviocytes (FLS) play an important role in the pathogenesis of rheumatoid arthritis (RA) through participating in joint tissue inflammation and joint damage. MicroRNAs are a kind of small non-coding RNAs that can regulate gene expression in the transcription level to affect cell behaviors. This study intended to investigate the expression of miR-19 in FLS from RA patients and related mechanism. A total of 126 RA patients were selected in this study. MiR-19 expression in FLS was detected by qRT-PCR. Toll like receptor 2 (TLR2) protein expression was tested by Western blot. MiR-19 target genes were confirmed by bioinformatics analysis and luciferase reporter assay. The impact of miR-19 on the expression of TLR2, interleukin 6 (IL-6), and matrix metalloproteinase 3 (MMP-3) in FLS were analyzed by cell transfection and Western blot. MiR-19 expression in FLS from RA patients was significantly downregulated compared with control (P < 0.05), while TLR2 level was increased (P < 0.05). Bioinformatics analysis and luciferase reporter assay confirmed that TLR2 was the target gene of miR-19. Transfection of miR-19 mimic or miR-19 inhibitor obviously suppressed or increased TLR2 expression, and reduced or promoted release of cytokines IL-6 and MMP-3 in FLS, respectively. In conclusion, MiR-19 expression was downregulated in FLS from RA patients, leading to increased TLR2 expression and enhanced cytokines release.
27747537 Biologics Prescribing for Rheumatoid Arthritis in Older Patients: A Single-Center Retrospe 2015 Dec INTRODUCTION: Appropriate medical treatment can reduce the morbidity and mortality associated with rheumatoid arthritis (RA). Studies have shown that older patients with RA may be treated less aggressively than their younger counterparts, despite evidence suggesting that biologic treatments may be safe and efficacious in older age groups. The aim of this study was to assess whether patient age was associated with biologic treatment for RA in a single center in the United Kingdom. METHODS: This was a retrospective cross-sectional analysis of clinic records for all patients with RA reviewed over 1 year in our center. Data were also collected on healthcare use in patients aged 65 years and older as a surrogate marker of comorbidity. RESULTS: In total, 856 patients with RA were identified, of which 22.8% were on biologic treatment. Patients on biologics were younger (mean age 58.9 years) compared to the mean age of all patients (61.4 years). Of patients aged less than 65 years, 27.2% were receiving biologic treatment, while only 15.2% of patients aged 65 years or older were on biologics. Increasing age was significantly associated with a lower likelihood of receiving biologic treatment. However, in patients 65 years or older, there was no significant difference in overall healthcare use between those on biologic treatment and those not. Patients treated with prednisolone were found to have a greater number of admissions. CONCLUSION: In our center, older patients are less likely to receive biologic treatment than younger patients. Among older patients we found no difference in healthcare use between those treated with biologics and those not, suggesting similar levels of comorbidity. Potential contributors are discussed, but further assessment is required to determine the reasons for this observation.