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ID PMID Title PublicationDate abstract
31430553 The association between genetic polymorphisms of interleukin 23 receptor gene and the risk 2020 Jan This meta-analysis was conducted to confirm whether seven single nucleotide polymorphisms (SNPs) of interleukin-23 receptor (IL23R) gene are associated with rheumatoid arthritis (RA) susceptibility. RevMan version 5.3 was used to calculate statistical data. Sixteen articles involving 11,816 RA patients and 14,268 healthy controls were included in this meta-analysis. A significant association was identified between the rs11209026 polymorphism and RA susceptibility in Caucasians (AA vs. GG: OR = 1.78, 95% CI = 1.02-3.10, P = .04; AA vs. AG + GG: OR = 1.77, 95% CI = 1.02-3.08, P = .04). Additionally, our result showed that the G allele of IL23R/rs10489629 had a significantly increased frequency in RA patients of Caucasians and Asians (A vs. G: OR = 0.92, 95% CI = 0.88-0.97, P = .002; OR = 0.62, 95% CI = 0.44-0.87, P = .006, respectively). Furthermore, the meta-analysis revealed a significant association between the rs1343151 polymorphism and RA susceptibility in Caucasians (C vs. T: OR = 0.91, 95% CI = 0.87-0.96, P = .0004). Our meta-analysis confirmed the IL23R gene might be treated as a susceptible factor for RA.
31304659 Ultrasound power Doppler and gray scale joint inflammation: What they reveal in rheumatoid 2019 Sep AIM: Power Doppler (PD) and gray scale (GS) imaging are commonly employed during ultrasonography in rheumatoid arthritis (RA). While PD vascularity is often regarded as an ultrasound feature of more active joint inflammation, the true clinical significance of GS joint inflammation is less understood. We aimed to gain further insight into ultrasound PD and GS joint inflammation by studying their association with Disease Activity Score of 28 joints (DAS28) (a disease activity measure) and ultrasound-detected bone erosion (a structural damage measure). METHOD: In this cross-sectional study, ultrasound PD and GS joint inflammation were graded 0-3 (semi-quantitatively) and bone erosion was graded as yes = 1/no = 0 at each joint recess. Linear regression and Pearson correlation were used to characterize relationships and assess correlation of PD and GS scores with DAS28 and ultrasound erosion scores. RESULTS: One thousand and eighty joints and 1800 joint recesses from 36 peripheral joint sites (bilateral metacarpophalangeal joints, thumb interphalangeal joints, proximal interphalangeal joints, metatarsophalangeal joints, elbow, wrist and ankle) were scanned in 30 adult RA patients. PD scores correlated with DAS28 (r = 0.46, P = 0.0104) but not with ultrasound erosion scores; GS scores correlated with ultrasound erosion (r = 0.64, P = 0.0001) but not with DAS28 scores. Simple linear regression revealed PD as predictive of DAS28 (P = 0.0104) and GS as predictive of ultrasound-detected bone erosion (P = 0.0001). CONCLUSION: Ultrasound PD joint inflammation is associated with disease activity and is correlated with DAS28. In contrast, GS joint inflammation is associated with structural damage and is correlated with ultrasound-detected bone erosion.
31514073 Genotypic-Phenotypic Screening of Galectin-3 in Relation to Risk Towards Rheumatoid Arthri 2019 May CONTEXT: Galectin-3, a 35 kDa protein, is the only known member of chimera type galectin family. A growing body of evidences demonstrated the pro-inflammatory role of galectin-3 in the pathogenesis of Rheumatoid arthritis (RA). OBJECTIVES: Keeping in view the pivotal role of galectin-3 in pathogenesis of RA, the present case-control study was designed for genotypic and phenotypic screening of galectin-3 in RA. METHODS: A case-control association study recruited 200 RA patients and 200 age- as well as gender- matched (p >0.05) controls, after written informed consent. A total of eight SNPs were selected on the basis of in silico analysis, which were subjected to genetic analysis using different techniques. LD was calculated and different haplotypes were constructed. RESULTS: Significant association of three SNPs i.e. rs1009977, rs4644, and rs74050921 along with elevated galectin-3 levels were observed with susceptibility towards RA. Further, high prevalence of TACGTAGC haplotype were observed in RA patients. In addition to the studied SNPs, eight novel variants were also identified in the CRD region of LGALS3. Genotype phenotype correlation indicated significant elevated galectin-3 levels among different genotypes in rs1009977 and rs74050921. CONCLUSION: The findings of the present study may indicate the role of galectin-3 and its variants in pathogenesis of RA.
30992155 Obstetric outcomes in women with rheumatoid arthritis: Results from Nationwide Inpatient S 2019 Oct OBJECTIVE: Fertility is reduced in patients with Rheumatoid Arthritis due to unknown cause. Few studies have addressed pregnancy outcomes in RA. This study was undertaken to determine the frequency of complications occurring during pregnancy for women with RA and compare with the general obstetric population by using the largest inpatient care database. METHODS: By using the 2003-2011 Nationwide Inpatient Sample of Healthcare Cost and Utilization Project, we estimated the number of obstetric hospitalization in women with RA between the age group 18-50 years. Demographic characteristics and in-hospital obstetric complications for all pregnancy-related admissions for women with and without RA were compared. Multivariate logistic regression analysis was used to obtain adjusted odds ratio. RESULTS: The total number of obstetric hospitalization was 42.32 million of which 31,439 were women with RA. The maternal age of RA population was higher (30.5 years) than that in the control group (27 years). After adjusting for potential confounders, maternal RA population had a significantly higher prevalence of hypertensive diseases, premature rupture of membranes, antepartum hemorrhage, preterm delivery, intrauterine growth retardation and cesarean delivery. The prevalence of postpartum hemorrhage and the risk of inpatient mortality were not different between two groups. CONCLUSION: Women with RA have a higher risk of adverse outcomes of pregnancy and thus close antenatal and post-delivery monitoring need to be performed in order to reduce complications. Further studies are needed to examine these findings in relation to severity of disease, medications used and the presence of other comorbidities.
31451935 Nailfold capillaroscopy and autoimmune connective tissue diseases in patients from a Portu 2020 Feb Raynaud's phenomenon (RP) is frequent in autoimmune connective tissue diseases (AICTD) and its approach includes nailfold capillaroscopy (NFC), as it is a non-invasive technique that permits direct visualization of the microcirculation. The aim of this study is to analyze and establish clinical correlations between NFC findings and particular aspects of autoimmune disorders. This is a retrospective study. Clinical data from patients attending our NFC clinic were reviewed. Inclusion criteria included AICTD previous diagnosis, which included systemic sclerosis (SSc), mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), Sjögren syndrome, inflammatory idiopathic myopathies (IIM), rheumatoid arthritis, undifferentiated connective tissue disease and antiphospholipid syndrome (APS). Videocap(®) version 3.0 biomicroscope was used. NFC score was determined. For statistics, SPSS software was utilized. 384 patients were included; most of them were women, with mean age of 47 years. RP was present in 91% of the patients, with greater prevalence in SSc and MCTD. Scleroderma pattern was the most prevalent NFC pattern, mainly in SSc, MCTD and IIM. Mean capillary density was reduced in IIM, SSc and MCTD. NFC score was worse in SSc, IIM and MCTD. In patients with AICTD, RP is related to microvascular damage and worse NFC score. NFC scleroderma pattern correlates with SSc classification criteria score. In MCTD, scleroderma pattern relates to myositis. SLE and APS reveal significant hemorrhages, but not related to APS antibodies. This study highlights the possible role of NFC as biomarker of AICTD, particularly in SSc and IIM.
31312201 A Combined Transcriptomic and Genomic Analysis Identifies a Gene Signature Associated With 2019 Background: Rheumatoid arthritis (RA) is the most frequent autoimmune disease involving the joints. Although anti-TNF therapies have proven effective in the management of RA, approximately one third of patients do not show a significant clinical response. The objective of this study was to identify new genetic variation associated with the clinical response to anti-TNF therapy in RA. Methods: We performed a sequential multi-omic analysis integrating different sources of molecular information. First, we extracted the RNA from synovial biopsies of 11 RA patients starting anti-TNF therapy to identify gene coexpression modules (GCMs) in the RA synovium. Second, we analyzed the transcriptomic association between each GCM and the clinical response to anti-TNF therapy. The clinical response was determined at week 14 using the EULAR criteria. Third, we analyzed the association between the GCMs and anti-TNF response at the genetic level. For this objective, we used genome-wide data from a cohort of 348 anti-TNF treated patients from Spain. The GCMs that were significantly associated with the anti-TNF response were then tested for validation in an independent cohort of 2,706 anti-TNF treated patients. Finally, the functional implication of the validated GCMs was evaluated via pathway and cell type epigenetic enrichment analyses. Results: A total of 149 GCMs were identified in the RA synovium. From these, 13 GCMs were found to be significantly associated with anti-TNF response (P < 0.05). At the genetic level, we detected two of the 13 GCMs to be significantly associated with the response to adalimumab (P = 0.0015) and infliximab (P = 0.021) in the Spain cohort. Using the independent cohort of RA patients, we replicated the association of the GCM associated with the response to adalimumab (P = 0.0019). The validated module was found to be significantly enriched for genes involved in the nucleotide metabolism (P = 2.41e-5) and epigenetic marks from immune cells, including CD4+ regulatory T cells (P = 0.041). Conclusions: These findings show the existence of a drug-specific genetic basis for anti-TNF response, thereby supporting treatment stratification in the search for response biomarkers in RA.
31451934 Association of biomarkers of inflammation and HLA-DRB1 gene locus with risk of developing 2019 Dec Rheumatoid arthritis (RA) is an autoimmune disease causing chronic inflammation of the joints. Multiple factors, including HLA-DRB1 gene variants, influence the susceptibility to RA. The HLA-DRB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. In this study, we compared the inflammatory biomarkers values, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), between patients with RA and healthy control group of females of the Public Institution Health Centre of Sarajevo Canton. In addition, we estimated the frequencies of the HLA-DRB1 gene variants and their association with the risk for RA development in females. The haematological and biochemical tests were completed on automated analyzers. To assess the association between the HLA-DRB genes and the risk of RA in females, low-resolution genotyping of the HLA-DRB1, DRB3, DRB4, and DRB5 gene loci was performed by the sequence-specific polymerase chain reaction method (PCR-SSP). ESR and CRP were the most sensitive acute-phase reactants in females with RA and there was a correlation between ESR and CRP values in RA patients. There was significantly positive association between of the HLA-DRB1*03, *04, *08, *10, *11, and *14 variants and elevated values of ESR in RA patients, but negative between HLA-DRB1*03, *13 and *15 alleles and elevated CRP values. Furthermore, our results confirm genetic susceptibility to RA in a female population to the members of the HLA-DRB1*04 and *03 allelic groups, the DRB1*04/DRB1*04 and DRB1*03/DRB1*04 genotypes, and the DRB1*04-DRB4* or DRB1*03-DRB3* haplotypes, which, therefore, represent risk factors for the development of this disease. According to our results, the DRB1*01/DRB1*15 and DRB1*07/DRB1*16 genotypes and the HLA-DRB5 gene locus represent a protective factor for RA. The presence of specific HLA-DRB1 gene variants increases the risk of developing RA, while other variants provide protection against disease. Therefore, HLA typing could be helpful in the prediction of RA development and establishing and confirming a definitive diagnosis of autoimmune diseases in some subjects. A strong association with the higher levels of ESR and CRP could be used to establish definitive diagnosis and introduce of early treatment of RA to prevent the occurrence of RA symptoms.
30675683 The intensity of joint pain in relation to changes in serum TNFα during therapy with anti 2019 Aug INTRODUCTION: Tumor necrosis factor-alpha (TNFα) inhibitors have significantly improved the outcomes of treatment for rheumatoid arthritis (RA). In the present study, we aimed to determine whether serum levels of TNFα during therapy with TNFα inhibitors do really reflect the disease activity and correspond to the intensity of pain experienced. MATERIALS AND METHODS: Thirty RA patients were examined before and after 12 weeks of routine therapy with TNFα inhibitors. Serum levels of TNFα were measured with a high-sensitivity immunoassay and related to patients' clinical and biochemical status. Disease activity was assessed by the modified disease activity score (DAS28). RESULTS: A median relative change in TNFα was 13%. The patients were stratified according to whether the relative change in serum TNFα after therapy was above or below this median value. The patients from both subgroups did not differ in baseline characteristics and response to therapy. However, the patients in whom serum TNFα increased after therapy above the median value had more tender joints after treatment than patients from the other group. Consequently, the number of tender joints after the treatment correlated with absolute TNFα concentrations at this time (r = 0.37; p = 0.049) and the magnitude of changes in serum TNFα correlated with a change in the number of tender joints (r = - 0.48; p = 0.008). CONCLUSIONS: Circulating TNFα levels did not decrease in RA patients treated with TNFα inhibitors, despite clinical and biochemical improvement. It is possible, that circulating TNFα is responsible for the persistence of joint pain in this group of patients.
30835944 Amelioration of Autoimmune Arthritis in Mice Treated With the DNA Methyltransferase Inhibi 2019 Aug OBJECTIVE: Disease-associated, differentially hypermethylated regions have been reported in rheumatoid arthritis (RA), but no DNA methyltransferase inhibitors have been evaluated in either RA or any animal models of RA. The present study was conducted to evaluate the therapeutic potential of 5'-azacytidine (5'-azaC), a DNA methyltransferase inhibitor, and explore the cellular and gene regulatory networks involved in the context of autoimmune arthritis. METHODS: A disease-associated genome-wide DNA methylation profile was explored by methylated CpG island recovery assay-chromatin immunoprecipitation (ChIP) in arthritic B cells. Mice with proteoglycan-induced arthritis (PGIA) were treated with 5'-azaC. The effect of 5'-azaC on the pathogenesis of PGIA was explored by measuring serum IgM and IgG1 antibody levels using enzyme-linked immunosorbent assay, investigating the efficiency of class-switch recombination (CSR) and Aicda gene expression using real-time quantitative polymerase chain reaction, monitoring germinal center (GC) formation by immunohistochemistry, and determining alterations in B cell subpopulations by flow cytometry. The 5'-azaC-induced regulation of the Aicda gene was explored using RNA interference, ChIP, and luciferase assays. RESULTS: We explored arthritis-associated hypermethylated regions in mouse B cells and demonstrated that DNA demethylation had a beneficial effect on autoimmune arthritis. The 5'-azaC-mediated demethylation of the epigenetically inactivated Ahr gene resulted in suppressed expression of the Aicda gene, reduced CSR, and compromised GC formation. Ultimately, this process led to diminished IgG1 antibody production and amelioration of autoimmune arthritis in mice. CONCLUSION: DNA hypermethylation plays a leading role in the pathogenesis of autoimmune arthritis and its targeted inhibition has therapeutic potential in arthritis management.
31292564 Cardiometabolic comorbidities in RA and PsA: lessons learned and future directions. 2019 Aug Cardiometabolic comorbidities present a considerable burden for patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA). Both RA and PsA are associated with an increased risk of cardiovascular disease (CVD). PsA more often exhibits an increased risk of metabolically linked comorbidities such as obesity, insulin resistance, type 2 diabetes mellitus and non-alcoholic fatty liver disease. Although both RA and PsA are characterized by a state of chronic inflammation, the mechanisms that contribute to CVD risk in these conditions might not be identical. In RA, systemic inflammation is thought to directly contribute to CVD risk, whereas in PsA, adiposity is thought to contribute to a notable metabolic phenotype that, in turn, contributes to CVD risk. Hence, appropriate management strategies that consider the increased risk of cardiometabolic comorbidities in patients with inflammatory arthropathy are important. In RA, such strategies should focus on the prediction of CVD risk and its management through targeting chronic inflammation and traditional CVD risk factors. In PsA, management strategies should additionally focus on targeting metabolic components, including weight management, which might not only help improve disease activity in the joints, entheses and skin, but also reduce the risk of metabolic comorbidities and improve the quality of life of patients.
31056959 An updated review of glucocorticoid-related adverse events in patients with rheumatoid art 2019 Jul INTRODUCTION: Glucocorticoids represent a cornerstone in the treatment of rheumatoid arthritis. Their effect as a disease-modifying treatment in rheumatoid arthritis is well established. Despite this, the risk of adverse events of glucocorticoids, especially in high doses and over a long time, is constantly highlighted. Data on the prevalence and impact of glucocorticoid-related adverse effects in rheumatoid arthritis is needed, therefore, to be regularly revisited. AREAS COVERED: In this review, our primary aim was to provide an update of evidence from randomized controlled trials and observational cohort studies on the safety of glucocorticoid treatment in rheumatoid arthritis. Our secondary aim was to provide a critical overview of the concerns raised with both study designs - randomized clinical trials versus nonrandomized observational studies - regarding the assessment of the safety of glucocorticoids in rheumatoid arthritis. EXPERT OPINION: In the meantime, adherence to recommendations and consensus on standardized methodologies for monitoring and reporting adverse events is essential to improve our knowledge and competence in the best management of glucocorticoids.
31278101 Dose-response associations between metabolic indexes and the risk of comorbid type 2 diabe 2019 Jul 4 OBJECTIVE: To investigate whether there were any differences in the patterns of metabolic abnormalities between patients with rheumatoid arthritis (RA) with comorbid type 2 diabetes mellitus (T2DM) and other populations, and to plot the dose-response relationships between metabolic indexes and the risk of comorbid T2DM among patients with RA. DESIGN AND SETTING: This is a retrospective case-control study using electronic medical records (EMRs). Patients with RA and/or T2DM or controls who were admitted to the First Affiliated Hospital of China Medical University between April 2008 and December 2016 were retrospectively recruited through the EMR system. After age-matching and sex-matching, 261 controls, 274 patients with T2DM, 276 patients with RA and 151 patients with RA+T2DM were eventually recruited. RESULTS: Patients with RA+T2DM exhibited higher levels of systolic blood pressure (SBP), fasting plasma glucose (FPG) and triglyceride (TG) than the RA only patients. Moreover, the proportions of impaired fasting glucose (IFG), and total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) dyslipidaemia in the RA+T2DM group were higher than those in the RA alone group (for IFG: 28.48% vs 18.84%, p=0.02; for TC: 25.17% vs 15.22%, p=0.01; for LDL-C: 25.83% vs 17.03%; p=0.03). Rheumatoid factor (RF) positivity and IFG were independent risk indicators for comorbid T2DM among patients with RA (for RF positivity: OR=0.45; 95% CI: 0.29 to 0.69; p<0.001; for IFG: OR=1.70; 95% CI: 1.04 to 2.76; p=0.03). CONCLUSION: Linear dose-response associations between SBP, TC, TG and the risk of comorbid T2DM among patients with RA were observed, whereas a non-linear dose-response association between FPG and the risk of comorbid T2DM was found. Patients with RA+T2DM were more likely to exhibit metabolic abnormalities than RA only patients. Patients with RA+T2DM with metabolic abnormalities deserve more attention from rheumatologists and endocrinologists.
30423114 Genetic influences on susceptibility to rheumatoid arthritis in African-Americans. 2019 Mar 1 Large meta-analyses of rheumatoid arthritis (RA) susceptibility in European (EUR) and East Asian (EAS) populations have identified >100 RA risk loci, but genome-wide studies of RA in African-Americans (AAs) are absent. To address this disparity, we performed an analysis of 916 AA RA patients and 1392 controls and aggregated our data with genotyping data from >100 000 EUR and Asian RA patients and controls. We identified two novel risk loci that appear to be specific to AAs: GPC5 and RBFOX1 (PAA < 5 × 10-9). Most RA risk loci are shared across different ethnicities, but among discordant loci, we observed strong enrichment of variants having large effect sizes. We found strong evidence of effect concordance for only 3 of the 21 largest effect index variants in EURs. We used the trans-ethnic fine-mapping algorithm PAINTOR3 to prioritize risk variants in >90 RA risk loci. Addition of AA data to those of EUR and EAS descent enabled identification of seven novel high-confidence candidate pathogenic variants (defined by posterior probability > 0.8). In summary, our trans-ethnic analyses are the first to include AAs, identified several new RA risk loci and point to candidate pathogenic variants that may underlie this common autoimmune disease. These findings may lead to better ways to diagnose or stratify treatment approaches in RA.
30658609 Influence of seasonal changes on disease activity and distribution of affected joints in r 2019 Jan 18 BACKGROUND: Previous studies suggest that RA activity is sensitive to seasonal changes. This study explored the influence of season on RA activity, particularly the distribution of affected joints, using a nationwide database in Japan. METHODS: We investigated 12,839 patients whose RA activity was recorded in spring (n = 3250), summer (n = 916), fall (n = 1021), and winter (n = 7652). Disease activity score (DAS) 28-CRP, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were used as indices of disease activity. Disease activity was also assessed according to DAS28-CRP scores (remission, low, moderate, or high). The affected joint distribution was investigated using novel joint indices (x, y, z), where x and y are indices for the upper and lower joints, respectively, and z is the index for large joint predominance. RESULTS: Mean DAS28-CRP and median SDAI and CDAI scores were highest in spring and lowest in fall. There was a significant difference in the DAS28-CRP for fall versus spring and winter. Fall was associated with a higher remission rate, and spring and winter with high and moderate RA activity, respectively. Significant differences in x, y, SDAI, and CDAI scores were found for spring versus summer, fall, and winter, in addition to fall versus winter (except in y). There was no seasonal difference in the z index. CONCLUSIONS: RA activity in the upper and lower extremities may be highest in spring, followed by winter. Seasonal changes should be considered in patients with RA to better understand their symptoms.
31130038 Cumulative Rheumatic Inflammation Modulates the Bone-Vascular Axis and Risk of Coronary Ca 2019 Jun 4 Background Rheumatic diseases are related to both abnormal bone turnover and atherogenesis, but a mechanistic link was missing. Methods and Results We investigated the effect of cumulative rheumatic inflammation ( CRI ) on risk of coronary calcification in a retrospective cohort of 145 rheumatoid arthritis patients. A time-adjusted aggregate CRI score was derived by conglomerating all quarterly biomarker encounters of serum C-reactive protein over 60 months immediately preceding computed tomography coronary angiography. Flow cytometry was performed to measure the osteocalcin-positive ( OCN (+)) CD 34(+) KDR (+) and OCN (+) CD 34(+) circulating endothelial progenitor cells ( EPCs ). Conventional early circulating EPCs CD 34(+) CD 133(+) KDR (+) was determined. Coronary calcification was defined as any Agatston score >0. 50% of patients (n=72/145) had coronary calcification. CRI score was associated with presence of coronary calcification ( P=0.004) (multivariable-adjusted: highest versus lowest quartile: odds ratio=5.6 [95% CI 1.1-28.9], P=0.041). Receiver operating characteristics curve revealed divergent behavior of OCN -expressing circulating EPCs ( OCN (+) CD 34(+) EPCs : area under the curve=0.60, P=0.034; OCN (+) CD 34(+) KDR (+) EPCs : area under the curve=0.59, P=0.053, positive predictors) versus conventional early EPCs ( CD 34(+) CD 133(+) KDR (+): area under the curve=0.60, P=0.034, negative predictor) for coronary calcification, which persisted after multivariable adjustments ( OCN (+) CD 34(+) KDR (+) [>75th percentile]: odds ratio=7.2 [95% CI 1.8-27.9], P=0.005; OCN (+) CD 34(+) EPCs [>75th percentile]: odds ratio=6.0 [95% CI 1.5-23.3], P=0.010; CD 34(+) CD 133(+) KDR (+) [>75th percentile: odds ratio=0.3 [95% CI 0.1-1.0], P=0.053). Intriguingly, the CRI score was associated with increased OCN (+) CD 34(+) EPCs (highest versus lowest quartile: B=+25.6 [95% CI 0.8-50.5] [×10(3)/mL peripheral blood], P=0.043), but reduced CD 34(+) CD 133(+) KDR (+) EPCs (highest versus lowest quartile: B=-16.2 [95% CI -31.5 to -0.9], P=0.038). Conclusions Preceding 60 months of CRI is associated with increased risk of coronary calcification and altered OCN expression in circulating EPCs .
31272806 Risk of medical complications following total hip or knee arthroplasty in patients with rh 2020 Feb OBJECTIVE: To investigate the risk of medical complications following total hip and knee arthroplasty (THA/TKA) among rheumatoid arthritis (RA) compared with osteoarthritis (OA) patients; and, to assess the risk of complications among biologics-treated RA patients. METHODS: In a nationwide register-based study, patients with RA and OA with THA/TKA surgery between 2000 and 2015 were identified and followed up to 90 days after surgery for venous thromboembolism (VTE), myocardial infarction and stroke, and non-surgical infections, respectively. Information on treatment with biologics was obtained in the DANBIO rheumatology register to compare risks of complications with non-biologics treated. RESULTS: A total of 2899 and 112,571 patients with RA and OA had THA/TKA. RA was associated with a hazard ratio (HR) of 1.29 (1.03 to 1.61) for infection following THA/TKA, but a HR of 0.60 (0.26 to 0.98) for VTE following TKA. Biologics treated patients had a HR of 1.35 (0.65 to 2.80) for infection and 4.82 (1.67 to 13.90) for VTE compared with non-biologics treated RA patients. RA patients had no increased risk of post-surgical myocardial infarction and stroke (HR 1.16, 0.76 to 1.78) compared with OA, but a higher incidence proportion was observed in biologics treated compared with non-biologics treated (1.0% vs 0.6%); however, the number of events were too small to estimate a HR. CONCLUSION: In this study, RA was a risk factor for infection after THA/TKA, and RA patients treated with biologics had a slightly increased risk compared with non-biologics treated RA patients. Compared with OA, RA patients had a lower risk of VTE following THA/TKA, but our finding of increased incidences of VTE in biologics-treated patients warrants further studies.
29975015 Body Fat Percentage, Waist Circumference, and Obesity As Risk Factors for Rheumatoid Arthr 2019 Jun OBJECTIVE: To investigate the relationship between bioimpedance-derived total body fat percentage, waist circumference, and body mass index (BMI) and the subsequent development of rheumatoid arthritis (RA). METHODS: A population-based prospective cohort study was conducted using 55,037 patients enrolled in the Danish Diet, Cancer, and Health cohort. Baseline data included anthropometric measures and lifestyle factors. Individuals who developed RA were identified through linkage with the Danish National Patient Registry. The relationships between bioimpedance-derived body fat percentage, waist circumference, and BMI and incident RA were assessed using Cox proportional hazards regression models, stratifying by sex. All analyses were performed for overall RA and the serologic subtypes seropositive and other RA. RESULTS: A total of 210 men (37.6% with seropositive RA) and 456 women (41.0% with seropositive RA) developed RA during a median follow-up of 20.1 years. In women, the overall RA risk was 10% higher for each 5% increment of total body fat (hazard ratio [HR] 1.10 [95% confidence interval (95% CI) 1.02-1.18]), 5% higher for each 5-cm increment of waist circumference (HR 1.05 [95% CI 1.01-1.10]), and nearly 50% higher in those whose BMI was in the obese range compared to normal range BMI (HR 1.46 [95% CI 1.12-1.90]). These positive associations were also found for patients with other RA. In men, there were no clear associations between body fat percentage, waist circumference, or BMI and RA. No significant associations were found for seropositive RA in women or men, possibly related to low sample size. CONCLUSION: In women, higher body fat percentage, higher waist circumference, and obesity were associated with a higher risk of RA.
31812101 Phytochemicals targeting matrix metalloproteinases regulating tissue degradation in inflam 2020 Jan PURPOSE: Matrix metalloproteinases, zinc dependent proteolytic enzymes, have significant implications in extracellular matrix degradation associated with tissue damage in inflammation and Rheumatoid arthritis. Numerous orchestrated pathways affects instigation and blockade of metalloproteinases as well as various factors that increase the expression of MMPs including inflammatory cytokines, hormones and growth factors. Direct inhibition of these proteolytic enzymes or modulation of these pathways can provide protection against tissue destruction in inflammation and rheumatoid arthritis. Inclination towards use of plant derived phytochemicals to prevent tissue damage has been increasing day by day. Diversity of phytochemicals have been known to directly inhibit metalloproteinases. Hence, thorough knowledge of phytochemicals is very important in novel drug discovery. METHODS: Present communication evaluates various classes of phytochemicals, in effort to unveil the lead molecules as potential therapeutic agents, for prevention of MMPs mediated tissue damage in inflammation and rheumatoid arthritis. Data have been analyzed through different search engines. RESULTS: Numerous phytochemicals have been studied for their role as MMPs inhibitors which can be processed further to develop into useful drugs for the treatment of inflammation and rheumatoid arthritis. CONCLUSION: In search of new drugs, phytochemicals like flavonoids, glycosides, alkaloids, lignans & terpenes offer a wide canvas to develop into valuable forthcoming medicaments.
30984167 Targeting Activated Synovial Fibroblasts in Rheumatoid Arthritis by Peficitinib. 2019 Background: Synovial fibroblasts (SF) play a major role in the pathogenesis of rheumatoid arthritis (RA) and develop an aggressive phenotype destroying cartilage and bone, thus termed RASF. JAK inhibitors have shown to be an efficient therapeutic option in RA treatment, but less is known about the effect of JAK inhibitors on activated RASF. The aim of the study was to examine the effects of JAK inhibitors on activated RASF. Methods: Synovium of RA patients was obtained during knee replacement surgeries. Synoviocytes were isolated and pretreated with JAK inhibitors. Pro-inflammatory cytokines and matrix degrading proteinases were measured by ELISA in supernatant after stimulation with oncostatin M or IL-1β. The proliferation of RASF was measured by BrdU incorporation. Cell culture inserts were used to evaluate cell migration. For adhesion assays, RASF were seeded in culture plates. Then, plates were extensively shaken and adherent RASF quantified. Cell viability, cytotoxicity and apoptosis were measured using the ApoTox-Glo™ Triplex and the CellTox™ Green Cytotoxicity Assay. Results: Tofacitinib and baricitinib decreased the IL-6 release of RASF stimulated with oncostatin M. JAK inhibition attenuated the IL-6 release of IL-1β activated and with soluble IL-6 receptor treated RASF. In contrast, only peficitinib and filgotinib decreased the IL-6 release of RASF activated with IL-1β. Peficitinib decreased also the MMP-3, CXCL8, and CXCL1 release at 5 μM. Moreover, peficitinib was the only JAK inhibitor suppressing proliferation of activated RASF at 1 μM. Peficitinib further decreased the migration of RASF without being cytotoxic or pro-apoptotic and without altering cell adhesion. Conclusions: JAK inhibitors effectively suppress the inflammatory response induced by oncostatin M and by transsignaling of IL-6 in RASF. Only peficitinib modulated the IL-1β-induced response of RASF and their proliferation in vitro at concentrations close to reported Cmax values of well tolerated doses in vivo. In contrast to filgotinib, peficitinib also highly suppressed RASF migration showing the potential of peficitinib to target RASF.
30477351 Proliferation of rheumatoid arthritis fibroblast-like synoviocytes is enhanced by IL-17-me 2019 Jul Fibroblast-like synoviocytes (FLSs), with their tumor-like proliferation, play an important role in rheumatoid arthritis (RA), and interleukin-17 (IL-17) participates in RA pathology by affecting FLSs. The aims of this study were to investigate the effects of IL-17 on the proliferation and autophagy of FLSs and the role of signal transducer and activator of transcription-3 (STAT3) in RA. FLSs were treated with IL-17 at different concentrations (0, 1, 10, and 20 ng/mL); then, autophagy was assayed with western blotting, immunofluorescence, and transmission electron microscopy. The effects of IL-17 on FLSs proliferation were measured with the Cell Counting Kit-8 assay and flow cytometry to analyze cell cycle distribution, and proliferating cell nuclear antigen (PCNA) was detected by western blotting. The autophagy inhibitors, 3-methyladenine (3-MA) and chloroquine (CQ), were used to determine the effect of autophagy on proliferation in IL-17-treated FLSs. Finally, the STAT3 inhibitor STA21 was used to examine the relationship between STAT3 and autophagy in IL-17-treated FLSs. Our results showed that IL-17 positively affected autophagy and proliferation in FLSs. Inhibition of autophagy suppressed the IL-17-mediated proliferation of FLSs. Additionally, suppression of STAT3 activation decreased autophagy in IL-17-treated FLSs. Our findings showed that IL-17 promoted the tumor-like proliferation of FLSs by upregulating autophagy via STAT3 activation.