Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 27142240 | Impact of methotrexate dose on efficacy of adalimumab in Japanese patients with rheumatoid | 2017 Jan | OBJECTIVE: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16 mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice. METHOD: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10 mg/week or more (MTX ≥10 mg group) and <10 mg/week (MTX <10 mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria. RESULTS: The MTX ≥10 mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10 mg group (26.1%). Multivariate analysis showed that MTX ≥10 mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX ≥10 mg group compared with 52.0% in MTX <10 mg group. Discontinuation of ADA due to adverse events were comparable in the MTX ≥10 mg and MTX <10 mg groups (11.1% vs. 12.0%). CONCLUSIONS: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX ≥10 mg in Japanese RA patients. | |
| 28913574 | The association between the lymphocyte-monocyte ratio and disease activity in rheumatoid a | 2017 Dec | The lymphocyte-monocyte ratio (LMR) is a systemic inflammatory marker for prediction of disease development, progress, and survival. Recently, a genome-wide association study identified genetic variations in ITGA4 and HLA-DRB1 that affect the LMR levels and were widely believed to be susceptibility genes for autoimmune diseases, including rheumatoid arthritis (RA). However, the role of LMR in RA patients remains unclear. The LMR level and other laboratory data of 66 RA patients, 163 osteoarthritis (OA) patients, and 131 healthy controls (HC) were compared using binary logistic regression. The correlations between LMR and disease activity and other inflammatory markers were measured using the Spearman rank test. ROC curve analyses assessed the diagnostic accuracy of LMR in RA. The LMR and lymphocyte count were significantly lower in RA patients, whereas the monocyte count was significantly higher relative to the HC group/OA patients (p < 0.01). A decreased LMR has been associated with increased disease activity (p = 0.012). In addition, the DAS28 and traditional inflammatory markers, including ESR, CRP, RDW, PLR, and NLR, and immune-related factors, such as C4, IgA, and IgM, were inversely correlated with LMR, while hemoglobin and albumin were positively correlated with LMR. The ROC curve showed that the area under the curve of LMR was 0.705 (95%CI = 0.630-0.781). The corresponding specificity and sensitivity were 82.82 and 45.45%, respectively. The present study shows that the LMR is an important inflammatory marker which could be used to identify disease activity in RA patients and to distinguish RA from OA patients. | |
| 29158166 | The association between caspase-5 gene polymorphisms and rheumatoid arthritis in a Chinese | 2018 Feb 5 | Genetic factors are widely recognized to have a substantial effect on the susceptibility to rheumatoid arthritis (RA). We examined the contribution of caspase-5 (CASP5) gene polymorphisms to RA risk in a Chinese population. We conducted a case-control study involving 500 RA patients and 500 controls and performed co-expression analysis to identify genes associated with CASP5. We attempted to analyze the functions of these genes by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. We carried out genotyping using a custom-by-design 48-Plex SNP (single nucleotide polymorphism) Scanâ„¢ Kit. The independent effects of these genetic loci were evaluated by creating genetic risk scores (GRS). Bioinformatics analysis confirmed that CASP5 was related to the development of inflammation, which is the main feature of RA. In addition, the CASP5 rs9651713 polymorphism was associated with an increased risk of RA, but there was no significant association between any other tested polymorphism (rs2276414, rs2282657, rs3181171, rs3181318, rs3181175, rs3181337, and rs552217) and RA risk. In addition, a high GRS was positively correlated with the risk of RA. In conclusion, CASP5 may contribute to the development of RA by mediating inflammation. Larger studies with more diverse ethnic populations are needed to confirm these results. | |
| 28729325 | Risk of sarcoidosis and seropositive rheumatoid arthritis from occupational silica exposur | 2017 Jul 20 | OBJECTIVE: To study the impact of occupational silica exposure on the incidence rates of sarcoidosis and rheumatoid arthritis (RA) in a cohort of exposed workers in Swedish iron foundries. DESIGN: The prevalence of sarcoidosis and RA in a cohort of silica exposed workers was compared with the prevalence in the general Swedish population in this register study. A mixed model was used to calculate silica exposure, and individual silica exposures were used to compute dose responses. SETTING: Personnel records from 10 iron foundries were used to identify workers whose employment began before 2005 which was then linked to the national non-primary outpatient visits register. PARTICIPANTS: The final cohort consisted of 2187 silica-exposed male workers who had been employed for at least 1 year and were still alive without having emigrated when the follow-up study began. The cohort's employment period covers 23 807 person-years at risk. MAIN OUTCOME: The presented results indicate that moderate to high levels of silica exposure increase risks for sarcoidosis and seropositive RA. RESULTS: Mean levels of airborne silica dust in the foundries decreased significantly between the 1970s and 2000s. Incidence rates of sarcoidosis (3.94; 95% CI 1.07 to 10.08) and seropositive RA (2.59; 95% CI 1.24 to 4.76) were significantly higher among highly exposed individuals. CONCLUSION: Our results reveal increased risks for sarcoidosis and seropositive RA among individuals with high exposure to silica dust (>0.048 mg/m(3)) compared with non-exposed and less-exposed groups. | |
| 28460767 | Predictors of endothelial dysfunction and atherosclerosis in rheumatoid arthritis in India | 2017 Mar | OBJECTIVE: Cardiovascular (CV) disease is leading cause of mortality in rheumatoid arthritis (RA). Dysfunction of the vascular endothelium is a hallmark of most conditions that are associated with atherosclerosis and is therefore an early feature in atherogenesis. Biomarkers for rapid evolution of CV complications would be highly desirable for risk stratification. Finally, predictive biomarkers for cardiovascular risk would allow tailoring therapy to the individual. We assessed endothelial function and atherosclerosis utilizing carotid intima-media thickness (CIMT) in RA in context of clinical and laboratory markers in Indian RA population. METHODS: We performed a prospective study of 35 consecutive RA patients and 25 age- and sex matched healthy controls. Patients with traditional CV risk factors were excluded. Flow mediated dilatation (FMD) as measures of endothelial function and CIMT as measures of atherosclerosis were assessed. Disease-specific measures, inflammatory measures, serum cytokines, serum nitrite, lipids and endothelial progenitor cells (EPCs) were estimated. RESULTS: FMD was significantly lower in RA (6.53%±1.81%) compared to controls (10.77%±0.53%; p<0.001). CIMT (mm) was significantly increased in RA (0.62±0.17) vs. controls (0.043±0.07; p=0.003). In RA patients, FMD% inversely correlated with CIMT, CRP, DAS-28, TNF-α, serum nitrite and positively correlated with EPC. CIMT correlated with age, DAS-28, IL-6, HDL, LDL, and inversely correlated with EPC. CONCLUSIONS: In the present study, FMD and CIMT were impaired in RA, indicating endothelial dysfunction and accelerated atherosclerosis respectively. CRP, TNF-α, serum nitrite, DAS-28 and depleted EPC population predicted endothelial dysfunction. Age, IL-6, HDL, LDL and depleted EPC population predicted accelerated atherosclerosis. | |
| 27597652 | Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator o | 2017 Mar | OBJECTIVES: Tristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP. METHODS: The expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP. RESULTS: TTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation. CONCLUSIONS: The phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments. | |
| 28849205 | Modulation of the immune response in rheumatoid arthritis with strategically released rapa | 2017 Oct | Rheumatoid arthritis (RA) is a chronic inflammatory disease, which is associated with symptoms, including synovial membrane inflammatory pain, joint synovitis and stiffness. However, there are no effective methods available to cure this disease. In the present study, rapamycin was used to modulate immunity in RA. To limit the cytotoxicity of rapamycin, rapamycin was loaded into well‑characterized biocompatible nanoparticles. In vitro, rapamycin particles downregulated the activation of dendritic cell surface markers, including CD80+ and CD40+, upon interacting with macrophages. The rapamycin particles reduced the secretion of inflammatory cytokines, including interleukin (IL)‑6, tumor necrosis factor (TNF) and IL‑1β, which are characteristic of RA. In vivo, the rapamycin particles decreased the symptoms of RA in mice, and the production of inflammatory cytokines was associated with the occurrence of RA. The present study partially revealed the interactions between rapamycin and two types of immune cell in RA disease, and may potentially offer a solution to improve the treatment of RA. | |
| 27452207 | Evidence-based recommendations for the diagnosis and management of rheumatoid arthritis fo | 2017 Sep | AIM: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease leading to joint damage, functional disability, poor quality of life and shortened life expectancy. Early diagnosis and aggressive treatment are a principal strategy to improve outcomes. To provide best practices in the diagnosis and management of patients with RA, the Thai Rheumatism Association (TRA) developed scientifically sound and clinically relevant evidence-based recommendations for general practitioners, internists, orthopedists, and physiatrists. METHODS: Thirty-seven rheumatologists from across Thailand formulated 18 clinically relevant questions: three for diagnosis, 10 for treatments, four for monitoring, and one for referral. A bibliographic team systematically reviewed the relevant literature on these topics up to December 2013. A set of recommendations was proposed based on the results of systematic reviews combined with expert opinions. Group consensus was achieved for all statements and recommendations using the nominal group technique. RESULTS: A set of recommendations was proposed. For diagnosis, either American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism 2010 classification criteria can be applied. For treatment, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs, including antimalarials, methotrexate and sulfasalazine are recommended. Physiotherapy should be suggested to all patients. Tight control strategy and monitoring for efficacy and side effects of treatments, as well as indications for referral to a rheumatologist are provided. CONCLUSIONS: These evidence-based recommendations provide practical guidance for diagnosis, fundamental management and referral of patients with RA for non-rheumatologists. However, it should be incorporated with clinical judgments and decisions about care for each individual patient. | |
| 28192374 | Transcription factor NFAT5 promotes macrophage survival in rheumatoid arthritis. | 2017 Mar 1 | Defective apoptotic death of activated macrophages has been implicated in the pathogenesis of rheumatoid arthritis (RA). However, the molecular signatures defining apoptotic resistance of RA macrophages are not fully understood. Here, global transcriptome profiling of RA macrophages revealed that the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5) critically regulates diverse pathologic processes in synovial macrophages including the cell cycle, apoptosis, and proliferation. Transcriptomic analysis of NFAT5-deficient macrophages revealed the molecular networks defining cell survival and proliferation. Proinflammatory M1-polarizing stimuli and hypoxic conditions were responsible for enhanced NFAT5 expression in RA macrophages. An in vitro functional study demonstrated that NFAT5-deficient macrophages were more susceptible to apoptotic death. Specifically, CCL2 secretion in an NFAT5-dependent fashion bestowed apoptotic resistance to RA macrophages in vitro. Injection of recombinant CCL2 into one of the affected joints of Nfat5+/- mice increased joint destruction and macrophage infiltration, demonstrating the essential role of the NFAT5/CCL2 axis in arthritis progression in vivo. Moreover, after intra-articular injection, NFAT5-deficient macrophages were more susceptible to apoptosis and less efficient at promoting joint destruction than were NFAT5-sufficient macrophages. Thus, NFAT5 regulates macrophage survival by inducing CCL2 secretion. Our results provide evidence that NFAT5 expression in macrophages enhances chronic arthritis by conferring apoptotic resistance to activated macrophages. | |
| 29212515 | Psychometric properties of morning joint stiffness duration and severity measures in patie | 2017 Dec 6 | BACKGROUND: To assess the measurement properties of two single-item patient-reported outcome (PRO) measures that assessed the length of time (in minutes) and severity of morning joint stiffness (MJS) experienced each day. METHODS: Data from two Phase 3, randomized placebo-controlled (and active-controlled [RA-BEAM]), clinical studies assessing the safety and efficacy of baricitinib in adults with moderately to severely active rheumatoid arthritis (RA) were used to evaluate the psychometric properties of the Duration of MJS and Severity of MJS PROs. RESULTS: Test-retest reliability of Duration of MJS and Severity of MJS was supported through large intraclass correlation coefficients among stable patients (coefficient range for both studies: 0.88 to 0.93). In support of construct validity, moderate correlations were evidenced between Duration of MJS and other related patient- and clinician-reported assessments of RA symptoms and patient functioning, whereas moderate-to-strong correlations were evidenced between these same patient- and clinician-reported assessments and Severity of MJS. Statistically significant differences between the median and mean values of Duration of MJS and Severity of MJS for differing categories of RA disease severity supported known-groups validity. Finally, large and statistically significant differences in change scores from Day 1 to Week 12 for patients defined as responders versus non-responders using the American College of Rheumatology 20 criteria supported the responsiveness of both PROs. CONCLUSION: Duration of MJS and Severity of MJS PROs demonstrated reliability, validity, and responsiveness in adults with moderately to severely active RA, supporting the measurement of these key symptoms in clinical trials. | |
| 28173856 | Polymorphism and protein expression of MUTYH gene for risk of rheumatoid arthritis. | 2017 Feb 7 | BACKGROUND: We have previously described the association between rheumatoid arthritis (RA) prevalence and the two mutY Homolog (E. coli) (MUTYH) SNPs (rs3219463 and rs3219476) among the Taiwanese population. This present study will aim to elucidate whether the SNPs can alter the expression of EGFR in the progression of RA. METHODS: The cohort study included 368 Taiwan's Han Chinese RA patients and 364 healthy controls. Blood samples collected from the participants were analyzed to determine their serum MUTYH levels and to identify rs3219463 SNP of MUTYH from their genomic DNA. RESULTS: Our data resulted in a statistically significant difference in genotype frequency distributions at rs3219463 for RA patients and controls (p < 0.0002). Also, the patients with G carrier at rs3219463 were less likely to suffer from painful joints (p < 0.006) and DAS28 scores (p < 0.003). Furthermore, the increase in serum level of MUTYH was also observed in RA patients (p < 0.005). CONCLUSIONS: Our study showed that RA is associated with rs3219463 SNP in EGFR gene and an increased serum level of the MUTYH protein. These findings suggest MUTYH is worthy of further investigation as a therapeutic target for RA. | |
| 29149783 | Hematological Improvement of Patients with Active Rheumatoid Arthritis by β-D-Mannuronic | 2017 Oct | The aim of this study was to investigate the effect of β-D-mannuronic acid (M2000) on hematological parameters in patients with active rheumatoid arthritis. This study was conducted on 25 patients with active rheumatoid arthritis (RA) (identifier: IRCT2014011213739N2). M2000 was administered orally for anemic and non-anemic RA patients at a dose of 500 mg twice daily for 12 weeks. The patients were permitted to continue the conventional treatments excluding NSAIDs. Blood samples were collected at baseline, 4 and 12 weeks after drug administration and were tested for hematological parameters. Moreover, serum levels of TNF-α and IL-6 were analysed before and after M2000 therapy compared to healthy controls using enzyme linked immunosorbent assay method. We found a significant increase in the count of red blood cells and also hemoglobin (Hb) concentration (0.9 g/dL) in anemic patients after 12 weeks of M2000 therapy (p<0.02 and p<0.01, respectively). Furthermore, our results showed an improvement in Hb level (0.45 g/dL) even in non-anemic patients who were treated by M2000 (p<0.04). The leukocytosis in RA patients, significantly decreased in both anemic and non-anemic patients after 12 weeks of M2000 therapy (p<0.02 and p<0.03, respectively). The percent of neutrophils significantly increased in anemic patients (p<0.01) while in non-anemic patients it significantly decreased after 12 weeks of M2000 therapy (p<0.01). The serum levels of IL-6 and TNF-α significantly decreased after 12 weeks of M2000 therapy (p<0.01 and p<0.04, respectively). M2000 improves hematological parameters in RA patients by its potent inhibitory effect on serum levels of TNF-α and IL-6. | |
| 29235242 | The effect of an educational intervention, based on clinical simulation, on the diagnosis | 2018 Mar | OBJECTIVE: The aim of the present study was to evaluate the effectiveness of an educational tool for general physicians, based on rheumatological clinical simulation, for the diagnosis of rheumatoid arthritis and osteoarthritis. METHODS: A randomized clinical study was carried out, in which the physician research subjects were assigned to one of two groups: the experimental group (educational intervention for rheumatoid arthritis with clinical simulation) or the control group (educational intervention for the basic aspects of the diagnosis and treatment of osteoporosis). Four weeks after the educational intervention, the members of both groups completed an examination that included four clinical cases with real patients, two clinical cases with two clinical simulation models and six virtual clinical cases. In this examination, the participants noted clinical findings, established a diagnosis and defined the complementary tests they would request, if necessary, to corroborate their diagnosis. RESULTS: A total of 160 doctors participated (80 in the active educational intervention for rheumatoid arthritis and 80 in the control group), of whom 89 were women (56%). The mean age was 35 (standard deviation 7.7) years. Success was defined as a physician correctly diagnosing at least 10 of the 12 cases presented. A significant difference of 81.3% (95% confidence interval 72-90%; p < 0.001) in success was found in favour of the active group (88.8% versus 7.5%). A greater number of correct answers was found in the active group compared with the control group in the detection of clinical findings and in the number of complementary tests requested (p < 0.001). CONCLUSIONS: The study showed the effectiveness of an educational intervention based on clinical simulation to improve the diagnostic approach to rheumatoid arthritis and osteoarthritis. The results open a new horizon in the teaching of rheumatology. | |
| 26862118 | Experiences of Patients With Rheumatoid Arthritis: A Qualitative Study. | 2017 Jun | Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that greatly impacts one's physical and psychosocial well-being. The purpose of this study was to explore the experiences and support needs of adult patients living with RA. A descriptive qualitative study was conducted, and 16 adults with RA were interviewed from October 2013 to January 2014. The transcribed data were analyzed using thematic analysis. Five themes were identified: altered physical capacity and well-being, psychological and emotional challenges, changes in social life, coping strategies, and support received and further support needs. This study provided insights into the experiences and support needs of patients with RA in Singapore. Physical and psychosocial challenges experienced by patients affected their daily and social activities. Patients' needs for variety of support should be addressed. | |
| 28891302 | Gastrocnemius Contracture in Patients With Rheumatoid Arthritis. | 2017 Dec | BACKGROUND: Rheumatoid arthritis is a chronic disease affecting multiple joints of the body. More than 90% of patients affected by rheumatoid arthritis develop foot or ankle pain over the course of their disease. The purpose of the current study was to report ankle dorsiflexion in rheumatoid arthritis patients as well as a control group utilizing a validated measurement instrument. METHODS: Using a previously validated device, 70 patients presenting with rheumatoid arthritis and 70 controls were measured for ankle range motion and isolated gastrocnemius contractures. Clinical and goniometer measurement of ankle range of motion was also performed. RESULTS: The rheumatoid arthritis group had a mean dorsiflexion of 12.3 degrees compared to a mean of 17.3 degrees in the control group ( P < .05). The difference in dorsiflexion was significantly less utilizing a goniometer than using the validated device, which may be due to measurement technique and external landmarks ( P < .05). CONCLUSION: Patients with rheumatoid arthritis had less ankle dorsiflexion than the control group. The clinical significance of this study is that it provides evidence that patients with rheumatoid arthritis have decreased ankle dorsiflexion even despite a lack of foot and ankle pain. In light of the high lifetime incidence of foot and ankle pain in these patients, this study provides some evidence that the decreased ankle dorsiflexion may be a contributing factor in foot and ankle pain, but further studies are needed. LEVEL OF EVIDENCE: Level II, prospective cohort study. | |
| 28738816 | Disease activity, resilience and health-related quality of life in Chinese patients with r | 2017 Jul 24 | BACKGROUND: Positive psychological constructs that can moderate or mediate the negative impact of disease activity on health-related quality of life (HRQOL) in patients with rheumatoid arthritis (RA) have not been explored widely. This study aimed to assess the associations of disease activity, resilience with HRQOL and the moderating and mediating roles of resilience among Chinese RA patients. METHODS: A multi-center, cross-sectional study was conducted in RA inpatients in northeast of China. A total 298 subjects completed the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and Ego-Resiliency Scale (ERS) to measure HRQOL and resilience. For the SF-36, physical function, physical role limitation, bodily pain and general health perception are gathered into physical component summary (PCS), while vitality, social functioning, emotional role limitation and mental health are gathered into mental component summary (MCS). Disease activity was evaluated by the Disease Activity Score 28-C-reactive protein (DAS28-CRP). Hierarchical regression analysis was applied to examine the associations of disease activity, resilience and the disease activity*resilience interaction with PCS and MCS, respectively. Asymptotic and resampling strategies were utilized to examine the mediating role of resilience. RESULTS: The mean scores of PCS and MCS were 40.67 and 59.14, respectively. Disease activity was negatively associated with both PCS and MCS, and resilience was only positively associated with MCS. The disease activity*resilience interaction term were significantly associated with MCS (β = 0.144, P = 0.003). The associations between disease activity and MCS were gradually reduced in low (1 SD below the mean, β = -0.369, P < 0.001), mean (β = -0.218, P < 0.001) and high (1 SD above the mean, β = -0.068, P = 0.369) groups of resilience. Resilience acted as a partial mediator in the disease activity-MCS association (effect size was -0.085, BCa 95% CI: -0.159, -0.028). CONCLUSIONS: Disease activity was negatively associated with both physical and mental HRQOL, and resilience was only positively associated with mental HRQOL. Resilience could attenuate and mediate the association between disease activity and mental HRQOL. In addition to controlling disease activity, targeted intervention strategies designed for resilience should be strengthened to improve the HRQOL of this population. | |
| 28399940 | Baseline JAK phosphorylation profile of peripheral blood leukocytes, studied by whole bloo | 2017 Apr 11 | BACKGROUND: We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4(+) T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA. METHODS: Thirty-five DMARD-naïve patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes. Treatment response was determined after 1 year of treatment with synthetic DMARDs, with remission defined as absence of tender and swollen joints and normal erythrocyte sedimentation rate. Exact logistic regression was used to investigate the association of baseline variables with treatment response. Ninety-five percent CIs of means were estimated by bias-corrected bootstrapping. RESULTS: High JAK3 phosphorylation in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes and low JAK2 phosphorylation in CD14(+) monocytes were significantly associated with remission following treatment with synthetic DMARDs. CONCLUSIONS: Baseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict treatment response achieved by synthetic DMARDs among patients with early RA. | |
| 28659665 | Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondy | 2017 | Tuberculosis (TB) still represents an important issue for public health in underdeveloped countries, but the use of antitumor necrosis factor agents (anti-TNF) for the treatment of inflammatory rheumatic disorders has reopened the problem also in countries with low TB incidence, due to the increased risk of TB reactivation in subjects with latent tuberculosis infection (LTBI). Over the last 5 years, several non-anti-TNF-targeted biologics have been licensed for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. We reviewed the epidemiology of TB, the role of different cytokines and of the immune system cells involved in the immune response against TB infection, the methods to detect LTBI, and the risk of TB reactivation in patients exposed to non-anti-TNF-targeted biologics. Given the limited role exerted by the cytokines different from TNF, as expected, data from controlled trials, national registries of biologics, and postmarketing surveillance show that the risk of TB reactivation in patients receiving non-anti-TNF-targeted biologics is negligible, hence raising the question whether the screening procedures for LTBI would be necessary. | |
| 29926646 | [Effects of TNF-alpha/NF-kappa B signaling pathway on etanercept alleviating rheumatoid ar | 2017 Apr 8 | OBJECTIVE: To investigate the effects of etanercept on collagen induced arthritis rats. METHODS: The rheumatoid arthritis model was established via subcutaneous injection of bovine type Ⅱ collagen, and the effects of etanercept was compared through three groups:①the normal control;②arthritis model treated with saline;③arthritis model treated with etanercept (0.5 mg/kg, intraperitoneal injection) with 10 rats in each group;group②and group③ were selected by arthritis index (≥ 2)and grouped randomly. The body weight and toe volume were measured at just before and during treatment weekly. Rats were sacrificed after 4 weeks of treatment, and the serum levels of tumor necrosis factor α(TNF-α), angiopoietin-1(Ang-1), IL-1β, IL-6 and IL-8 were tested by ELISA. Nuclear factor-kappa B(NF-κB) levels and subcellular locations in toe muscles were test by Western blot. RESULTS: Etanercept significantly relieved inflammation of rheumatoid arthritis, lowered the TNF-α and relative inflammatory factors levels compared with saline treatment (P<0.05). The results of Western blot showed that etanercept significantly suppressed the nuclear location of NF-κB p105/p50 caused by inflammation. CONCLUSIONS: The anti-inflammatation effect of etanercept may be related to its activity in inhibiting the activation of TNF-α/NF-κB pathway. | |
| 29325724 | Rheumatoid Arthritis, Disease Modifying Agents, and Periprosthetic Joint Infection: What D | 2018 Apr | The incidence of periprosthetic joint infection (PJI) among patients with rheumatoid arthritis (RA) is 1.6× greater than in patients undergoing the same procedure for osteoarthritis. This higher risk "may" be due to the immunosuppressive therapies for RA patients including corticosteroids, such as prednisone, and disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. There is a debate about the role of DMARDs in increasing the incidence of subsequent PJI. Studies show conflicting results, with some demonstrating no significant increase in the rates of PJI and some finding otherwise. The International Consensus Meeting on PJI recommended that DMARDs should be halted prior to an elective total joint arthroplasty based on their half-life. Moreover, the International Consensus Meeting stated that cessation of immunosuppressant medications should be performed in consultation with and under the direction of the treating physician. In this review, we aimed to provide an introduction to the available treatment options and cover the recommendations on the treatment protocols for RA patients who undergo elective total joint arthroplasty. |