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ID PMID Title PublicationDate abstract
32760165 Gene expression regulated by abatacept associated with methotrexate and correlation with d 2020 OBJECTIVES: Abatacept acts as a competitive inhibitor of the CD28/(CD80/86) costimulation signal required for T cell activation. Mechanisms of action of abatacept have not been fully investigated. The objective of this study was to provide detailed insight into the mode of action of Abatacept based on gene expression data. METHODS: In this ancillary study from the APPRAISE trial, we investigated the global molecular effects of Abatacept in whole blood samples collected prospectively in biologic naive rheumatoid arthritis patients (n = 19) at baseline and 6 months after the initiation of Abatacept therapy concomitant with methotrexate. Whole human genome microarrays (4x44K) were performed on both baseline and 6-month samples from responders and non-responders patients categorized according to EULAR criteria. T-test with Benjamini-Hochberg correction was performed to identify significant gene expression changes. Gene Ontology and Single Experiment Analysis tools allowed us to highlight specific biological mechanisms involved in methotrexate/Abatacept. RESULTS: In methotrexate/Abatacept responders, 672 genes were significantly (q<0.05) dysregulated at 6 months compared to baseline. Correlation analysis highlighted 19 genes whose dysregulations were significantly associated with disease activity variation (p<0.05) and whose functions were associated with proliferation, apoptosis of cells and mitochondrial metabolism, suggesting a restoration of oxidative signaling. The other 653 gene expression changes were relative to direct or indirect effects of methotrexate/Abatacept treatment and were significantly (p<0.005) involved in pathways relative to mRNA processing, proteasome, angiogenesis, apoptosis and TCR signaling. This study highlights new mechanisms of action of methotrexate/Abatacept and may provide new therapeutic targets to prevent autoimmunity in rheumatoid arthritis.
32143603 The inhibition by human MSCs-derived miRNA-124a overexpression exosomes in the proliferati 2020 Mar 6 BACKGROUND: Rheumatoid arthritis is a long-term, progressive autoimmune disease. It is characterized by synovial hyperplasia leading to swelling, stiffness, and joint deformity in more than one joint. Fibroblast-like synoviocytes are the major cell types that make up the synovial intima structure, which is one of the decisive factors in the development and course of rheumatoid arthritis. METHODS: The potential therapeutic effects of MSCs-derived miRNA-124a overexpression exosomes were evaluated in vitro by the method including MTT assay and cell cycle test for cell proliferation, scratch wound closure and transwell for cell migration, flow cytometry and western for the apoptosis detection. RESULTS: Exosomes derived from human MSCs that overexpression miRNA-124a were prepared and characterized. We found that the pretreatment of this exosome was able to inhibit the proliferation and migration of fibroblast-like synoviocyte cell line and promote the apoptosis of this cell during the co-incubation. CONCLUSIONS: Exosomes derived from MSCs were proved to be a suitable vector for the delivery of therapeutic miRNA-124a, and such miRNA-124a overexpression exosomes were expected to provide a new medicine and strategy for the treatment of rheumatoid arthritis.
32739894 Use of Disease-modifying Antirheumatic Drugs, Biologics, and Corticosteroids in Older Pati 2021 Jul OBJECTIVE: To examine changes in prescribing patterns, especially the use of corticosteroids (CS), in patients with rheumatoid arthritis (RA) over 2 decades. METHODS: This was a secondary analysis of health administrative data using a previously validated dataset and case definition for RA. Cases were matched 1:4 by age and sex to controls within a population of approximately 1 million inhabitants with access to universal health care. Longitudinal data for incident and prevalent RA cases were studied between 1997 and 2017. RESULTS: There were 8240 RA cases (all ≥ 65 yrs) with a mean (SD) age 72.2 (7.5) years and 70.6% were female. Over 20 years, annual utilization of coxibs in prevalent RA cases fell with a concomitant increase in disease-modifying antirheumatic drugs (DMARDs) and biologics. Over the same period, CS use was largely unchanged. Approximately one-third of patients had at least 1 annual prescription for CS, most frequently prednisone. The mean annual dose showed a modest reduction and the duration of utilization in each year shortened. Rheumatologists prescribed CS less frequently and in lower doses than other physician groups. For incident RA cases, there was a significant fall in annual prescribed dose of prednisone by rheumatologists over time. CONCLUSION: In older adults with RA, the utilization of DMARDs and biologics has increased over the past 20 years. However, the use of CS has persisted. Renewed efforts are required to minimize their use in the long-term pharmacological management of RA.
31257453 Impact of flare on radiographic progression after etanercept continuation, tapering or wit 2020 Jan 1 OBJECTIVES: The structural consequences of flare after dose reduction/discontinuation of biologic DMARDs in patients with RA who achieve remission are unclear. We compared the incidence of radiographic progression in patients with RA who did and did not experience flare after etanercept (ETN) reduction/withdrawal. METHODS: Eligible adults with moderately active RA despite MTX received ETN 50 mg plus MTX weekly in a 36-week, open-label induction period; patients achieving sustained low disease activity by week 36 were randomized to ETN 50 mg plus MTX, ETN 25 mg plus MTX, or placebo plus MTX in a 52-week, double-blind maintenance period. In post hoc analyses, radiographic progression (Δ modified total Sharp score ⩾0.5 units/year) was compared in patients with and without flare [based on DAS28 relapse (main analysis), and clinical disease activity index and simplified disease activity index relapse (sensitivity analyses)]. Findings from patients receiving full- and reduced-dose combination therapy were pooled for comparison with those from patients receiving MTX only. RESULTS: Significantly more patients receiving MTX monotherapy experienced flare, defined as DAS28 relapse (62% vs 21%; P < 0.0001) and radiographic progression (17% vs 9%; P < 0.001), than patients receiving full-/reduced-dose combination therapy in the double-blind period. Patients with flare defined as clinical disease activity index and simplified disease activity index relapse had higher rates of radiographic progression than those without flare in the full-/reduced-dose combination therapy group (P < 0.01). CONCLUSION: Radiographic progression may be a consequence of flare after biologic DMARD dose reduction/withdrawal in patients with RA. If these approaches are taken, careful monitoring for signs/symptoms of relapse is needed. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00565409.
32911717 Molecular and Cellular Mechanisms of Arthritis in Children and Adults: New Perspectives on 2020 Sep 8 Juvenile idiopathic arthritis and adult rheumatoid arthritis are two major groups with chronic joint pain and inflammation, extra-articular manifestations, and high risk of comorbidities, which can cause physical and ocular disability, as well as create great socio-economic pressure worldwide. The pathogenesis of arthritis manifested in childhood and adulthood is multifactorial, unclear, and overly complex, in which immunity plays an important role. Although there are more and more biological agents with different mechanisms of action for the treatment of arthritis, the results are not as expected, because there are partial responses or non-responsive patients to these compounds, high therapeutic costs, side effects, and so on; therefore, we must turn our attention to other therapeutic modalities. Updating knowledge on molecular and cellular mechanisms in the comparative pathogenesis of chronic arthritis in both children and adults is necessary in the early and correct approach to treatment. Photobiomodulation (PBM) represents a good option, offering cost-effective advantages over drug therapy, with a quicker, more positive response to treatment and no side effects. The successful management of PBM in arthritis is based on the clinician's ability to evaluate correctly the inflammatory status of the patient, to seek the optimal solution, to choose the best technology with the best physical parameters, and to select the mode of action to target very precisely the immune system and the molecular signaling pathways at the molecular level with the exact amount of quantum light energy in order to obtain the desired immune modulation and the remission of the disease. Light is a very powerful tool in medicine because it can simultaneously target many cascades of immune system activation in comparison with drugs, so PBM can perform very delicate tasks inside our cells to modulate cellular dysfunctions, helping to initiate self-organization phenomena and finally, healing the disease. Interdisciplinary teams should work diligently to meet these needs by also using single-cell imaging devices for multispectral laser photobiomodulation on immune cells.
32066556 Is the epidemiology of rheumatoid arthritis changing? Results from a population-based inci 2020 Apr OBJECTIVES: To examine trends in the incidence of rheumatoid arthritis (RA) from 2005 to 2014 overall and by serological status as compared with 1995-2004 and 1985-1994. METHODS: We evaluated RA incidence trends in a population-based inception cohort of individuals aged ≥18 years who first fulfilled the 1987 American College of Rheumatology (ACR) criteria for RA between 1 January 1985 and 31 December 2014. Incidence rates were estimated and were age-adjusted and sex-adjusted to the white population in the USA in 2010. Trends in incidence were examined using Poisson regression methods. RESULTS: The 2005-2014 incidence cohort comprised 427 patients: mean age 55.4 years, 68% female, 51% rheumatoid factor (RF) positive and 50% anti-cyclic citrullinated peptide antibody positive. The overall age-adjusted and sex-adjusted annual RA incidence in 2005-2014 was 41/100 000 population (age-adjusted incidence: 53/100 000 in women and 29/100 000 in men). While these estimates were similar to the 1995-2004 decade, there was a decline in the incidence of RF-positive RA in 2005-2014 compared with the previous two decades (p=0.004), with a corresponding increase in RF-negative cases (p<0.001). Smoking rates declined and obesity rates increased from earlier decades to more recent years. CONCLUSIONS: Significant increase in incidence of RF-negative RA and decrease in RF-positive RA in 2005-2014 compared with previous decades was found using 1987 ACR criteria. The incidence of RA overall during this period remained similar to the previous decade. The changing prevalence of environmental factors, such as smoking, obesity and others, may have contributed to these trends. Whether these trends represent a changing serological profile of RA requires further investigation.
32582191 Infectious Triggers in Periodontitis and the Gut in Rheumatoid Arthritis (RA): A Complex S 2020 Rheumatoid arthritis (RA) is a systemic immune mediated inflammatory disease of unknown origin, which is predominantly affecting the joints. Antibodies against citrullinated peptides are a rather specific immunological hallmark of this heterogeneous entity. Furthermore, certain sequences of the third hypervariable region of human leukocyte antigen (HLA)-DR class II major histocompatibility (MHC) molecules, the so called "shared epitope" sequences, appear to promote autoantibody positive types of RA. However, MHC-II molecule and other genetic associations with RA could not be linked to immune responses against specific citrullinated peptides, nor do genetic factors fully explain the origin of RA. Consequently, non-genetic factors must play an important role in the complex interaction of endogenous and exogenous disease factors. Tobacco smoking was the first environmental factor that was associated with onset and severity of RA. Notably, smoking is also an established risk factor for oral diseases. Furthermore, smoking is associated with extra-articular RA manifestations such as interstitial lung disease in anatomical proximity to the airway mucosa, but also with subcutaneous rheumatoid nodules. In the mouth, Porphyromonas gingivalis is a periodontal pathogen with unique citrullinating capacity of foreign microbial antigens as well as candidate RA autoantigens. Although the original hypothesis that this single pathogen is causative for RA remained unproven, epidemiological as well as experimental evidence linking periodontitis (PD) with RA is rapidly accumulating. Other periopathogens such as Aggregatibacter actinomycetemcomitans and Prevotella intermedia were also proposed to play a specific immunodominant role in context of RA. However, demonstration of T cell reactivity against citrullinated, MHC-II presented autoantigens from RA synovium coinciding with immunity against Prevotella copri (Pc.), a gut microbe attracted attention to another mucosal site, the intestine. Pc. was accumulated in the feces of clinically healthy subjects with citrulline directed immune responses and was correlated with RA onset. In conclusion, we retrieved more than one line of evidence for mucosal sites and different microbial taxa to be potentially involved in the development of RA. This review gives an overview of infectious agents and mucosal pathologies, and discusses the current evidence for causality between different exogenous or mucosal factors and systemic inflammation in RA.
31694748 The Comprehensive Rheumatologic Assessment of Frailty (CRAF): development and validation o 2020 May OBJECTIVES: Frailty is a topic that is gaining more and more interest in rheumatology. The aims of this study were to develop and preliminarily validate a frailty index dedicated to rheumatoid arthritis (RA) called the Comprehensive Rheumatologic Assessment of Frailty (CRAF). METHODS: Ten major frailty domains of CRAF were identified: nutritional status, weakness, falls, comorbidity, polypharmacy, social activity, pain, fatigue, physical function, and depression. Convergent validity was evaluated correlating the scores of the CRAF with the Frailty Instrument for Primary Care of the Survey of Health, Ageing and Retirement in Europe (SHARE-FI). Discriminant validity was assessed using receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression model procedure was used to assess the relative contribution of the individual determinants on the CRAF. RESULTS: Among the 219 RA patients, 79 (36.1%) were defined as non-frail (CRAF ≤0.12), 63 (28.8%) mild frail (0.12 0.36). In testing for convergent validity, a significant correlation was found between CRAF and SHARE-FI (p <0.0001). The discriminatory power of CRAF was higher than those of the SHARE-FI (difference between areas under the ROC curves=0.0853± 0.0282. Variables associated with frailty at the multivariate analysis were advanced age and high disease activity (both at p<0.0001). CONCLUSIONS: The CRAF demonstrated a robust validity and good discriminant accuracy. Implementation of the frailty assessment into the routine rheumatological practice could represent a major advance in RA care.
32141205 Who is afraid of biosimilars? Openness to biosimilars in an Australian cohort of patients 2020 Mar Biosimilars are increasingly adopted to improve affordability of biologics. An effective introduction of biosimilars requires an understanding of patient acceptance of these agents. We performed a cross-sectional study of 132 patients with rheumatoid arthritis prior to the introduction of biosimilar switching or prescribing in this cohort. Despite being unfamiliar with biosimilars, most patients are willing to accept biosimilar medicines if recommended by their rheumatologist. Patient concerns about biosimilar uptake mainly focus on concerns about its efficacy. There is a significant correlation between patient attitudes towards biosimilar and generic medicines.
32044136 Causal associations of iron status with gout and rheumatoid arthritis, but not with inflam 2020 Oct BACKGROUND & AIMS: We conducted a two-sample Mendelian randomization study to assess the associations of iron homeostasis with the risk of gout, rheumatoid arthritis and inflammatory bowel disease. METHODS: Single-nucleotide polymorphisms for iron status were selected at the genome-wide significance level from a large genome-wide association study of 48 972 European-descent individuals. Summary-level data for gout, rheumatoid arthritis and inflammatory bowel disease were obtained from The Global Urate Genetics Consortium and two large genome-wide association studies, respectively. Inverse-variance weighted method with random-effects and sensitivity analyses were performed. RESULTS: Genetic predisposition to high iron status was causally associated with higher odds of gout, lower odds of rheumatoid arthritis, but not associated with inflammatory bowel disease. The odds ratios of gout were 1.35 (95% confidence interval (CI), 1.00, 1.81; p = 0.047), 2.07 (95% CI, 1.23, 3.50; p = 0.006), 1.27 (95% CI, 1.07, 1.50; p = 0.007) and 0.69 (95% CI, 0.54, 0.90; p = 0.005) per one standard deviation increment of serum iron, ferritin, transferrin saturation, and transferrin levels, respectively. For rheumatoid arthritis, the corresponding odds ratios were 0.79 (95% CI, 0.65, 0.94; p = 0.010), 0.59 (95% CI, 0.40, 0.86; p = 0.007), 0.84 (95% CI, 0.75, 0.94; p = 0.003) and 1.28 (95% CI, 1.06, 1.55; p = 0.012). CONCLUSIONS: Based on consistent findings for four iron biomarkers, genetically high iron status was positively associated with gout and inversely associated with rheumatoid arthritis. There was limited MR evidence supporting a causal association between iron status and inflammatory bowel disease.
32411794 The Sufficient Immunoregulatory Effect of Autologous Bone Marrow-Derived Mesenchymal Stem 2020 Rheumatoid arthritis (RA) is an advanced autoimmune disease described by joint involvement. The special properties of mesenchymal stem cells (MSCs) introduced them as a potential therapeutic candidate for RA. In this study, a single dose of autologous MSCs isolated from bone marrow (autologous BM-MSCs, 1 × 10(6) per kg) was injected intravenously into 13 patients suffering from refractory RA who were followed up within 12 months after the intervention to evaluate immunological elements. Our results showed that the gene expression of forkhead box P3 (FOXP3) in peripheral blood mononuclear cells (PBMCs) considerably increased at month 12. We found a substantial increasing trend in the culture supernatant levels of IL-10 and transforming growth factor-beta 1 (TGF-β1) in PBMCs from the beginning of the intervention up to the end. Our data may reflect the sufficient immunoregulatory effect of autologous BM-MSCs on regulatory T cells in patients suffering from refractory RA.
33114390 DMARDs-Gut Microbiota Feedback: Implications in the Response to Therapy. 2020 Oct 24 Due to its immunomodulatory effects and the limitation in the radiological damage progression, disease-modifying antirheumatic drugs (DMARDs) work as first-line rheumatoid arthritis (RA) treatment. In recent years, numerous research projects have suggested that the metabolism of DMARDs could have a role in gut dysbiosis, which indicates that the microbiota variability could modify the employment of direct and indirect mechanisms in the response to treatment. The main objective of this review was to understand the gut microbiota bacterial variability in patients with RA, pre and post-treatment with DMARDs, and to identify the possible mechanisms through which microbiota can regulate the response to pharmacological therapy.
32774569 The Use of Oral Analgesics and Pain Self-Efficacy Are Independent Predictors of the Qualit 2020 OBJECTIVES: This study investigated the relationship between quality of life (QOL) and several factors, including pain assessments, in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional, single-center study enrolled 85 patients with RA. The variables investigated included demographic characteristics, the 28-joint disease activity score with C-reactive protein (DAS28-CRP), painDETECT questionnaire (PDQ), pain self-efficacy questionnaire (PSEQ), and pain catastrophizing scale (PCS). QOL was measured using the Japanese validated version of the European Quality of Life questionnaire with five dimensions and five levels (EQ-5D-5L). RESULTS: The use of oral steroids and oral analgesics was significantly associated with low EQ-5D-5L scores (P < 0.05). EQ-5D-5L score had a significant positive association with PSEQ (r = 0.414) and significant negative association with age, disease duration, DAS28-CRP, PDQ, and PCS (r = -0.217, -0.343, -0.217, -0.277, and -0.384, respectively). Multiple regression analysis showed that the use of oral analgesics and PSEQ were independent predictors of EQ-5D-5L score (β = -0.248, P < 0.05 and β = 0.233, P < 0.05). CONCLUSIONS: The use of oral analgesics by RA patients may influence their QOL, which, in turn, may affect their feelings of self-efficacy. Various pain management strategies, including surgical treatment, may be explored for the treatment of RA. Furthermore, the PSEQ may be a prominent part of the patient's overall assessment.
32142504 The Association Between MUC5B Mutations and Clinical Outcome in Patients with Rheumatoid A 2020 Mar 6 BACKGROUND Patients with rheumatoid arthritis (RA) who develop interstitial lung disease (RA-ILD), show features of usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT). This retrospective exploratory clinical study aimed to investigate the association between mutations in the MUC5B gene and clinical outcome in patients with RA, with or without RA-ILD, using whole-exome sequencing (WES). MATERIAL AND METHODS WES was performed using peripheral blood samples for mutations in the MUC5B gene in 51 patients diagnosed with RA without ILD, and 45 patients with RA-ILD. The cumulative incidence in acute exacerbations of RA-ILD and variables associated with acute exacerbations of RA-ILD were analyzed. RESULTS In patients with RA-ILD, the main genetic variants of MUC5B were identified, with an odds ratio (OR) of 3.410 (p=0.013). Nine patients with RA without ILD (17.6%) and 19 patients with RA-ILD (42.2%) expressed MUC5B variants. Patients with RA-ILD carrying MUC5B variants had a significantly increased duration of RA-ILD (p=0.03) and showed a UIP pattern on lung HRCT (p=0.01). Acute exacerbations of RA-ILD occurred in 25 patients during follow-up, including 13 patients with mutant MUC5B and 12 patients with wildtype MUC5B. Univariate analysis showed that MUC5B mutations (p=0.043), older age of onset of RA (p=0.041), increased serum anti-citrullinated protein antibodies (ACPAs) (p=0.033), and a UIP imaging pattern on HRCT (p=0.015) were significantly correlated with acute exacerbations of RA-ILD. However, these findings were not supported by multivariate analysis (p=0.065). CONCLUSIONS The carrier status of MUC5B variants was an indicator of reduced prognosis and increased exacerbations of RA-ILD.
31811747 Therapeutic potential of aryl hydrocarbon receptor ligands derived from natural products i 2020 Jun Rheumatoid arthritis is an autoimmune-mediated inflammatory disease, which is characterized by chronic synovitis, progressive bone destruction and reduced mobility. Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been shown to regulate the differentiation, activation and apoptosis of various cells involved in rheumatoid arthritis. The ligands of AhR such as tetrachlorodibenzo-p-dioxin, benzo[a]pyrene and 3,3'-diindolylmetheane are able to inhibit osteoclastogenesis and attenuate arthritis in mice. However, the long-term use of these compounds is associated with severe side effects, which limit their use as therapeutic agents in animals or humans. There is an urgent need to search for new AhR ligands that are effective and safe. This MiniReview discusses the potential therapeutic value of the AhR ligands derived from natural products.
32423969 Siblings of patients with rheumatoid arthritis have an increased mortality rate: a Swedish 2020 May OBJECTIVES: To estimate the mortality among siblings of patients with rheumatoid arthritis (RA) and put any excess mortality among these in relation to the mortality among patients with RA. METHODS: Using prospective nation-wide registers, we identified patients diagnosed with new-onset RA 2001-2017 (n=8137), patients with prevalent RA 2006-2017 (n=25 464), matched general population comparator subjects to all RA patients (n=22 457/68 674) and full-siblings of all groups (n=28 878/91 546).We followed all cohorts until death, 31 December 2018, migration and (for non-RA subjects) RA diagnosis. We compared patients with RA versus the general population, and siblings of RA versus siblings of the general population using Cox regression, including adjustment for socio-economy. RESULTS: The HR of death versus the general population was 1.11 (95% CI 1.01 to 1.22) for incident and 1.46 (95% CI 1.39 to 1.52) for prevalent patients with RA. The siblings of these patient groups were also at increased risk of death (HR=1.10, 95% CI 1.01 to 1.20 and 1.09, 95% CI 1.04 to 1.13, respectively), with little impact of adjustment for socio-economy. CONCLUSION: The mortality in RA is increased, but around one-fifth of this excess is present also among their siblings. Previous literature using general population rates for comparison has thus likely overestimated the direct impact on mortality attributable to RA. To bring down excess mortality in RA, optimal disease control is important but may not suffice.
33005097 Pain Mechanism in Rheumatoid Arthritis: From Cytokines to Central Sensitization. 2020 Pain is the most common symptom in patients with rheumatoid arthritis (RA). Although in recent years, through the implementation of targeted treatment and the introduction of disease-modifying antirheumatic drugs (DMARDs), the treatment of RA patients has made a significant progress, a large proportion of patients still feel pain. Finding appropriate treatment to alleviate the pain is very important for RA patients. Current research showed that, in addition to inflammation, RA pain involves peripheral sensitization and abnormalities in the central nervous system (CNS) pain regulatory mechanisms. This review summarized the literature on pain mechanisms of RA published in recent years. A better understanding of pain mechanisms will help to develop new analgesic targets and deploy new and existing therapies.
32667228 Elevated adiponectin predicts the development of rheumatoid arthritis in subjects with obe 2020 Nov Objective The aim of the current study is to determine whether baseline serum adiponectin levels predict the development of rheumatoid arthritis (RA). Method The current report includes 3693 individuals from the Swedish Obese Subjects (SOS) study. The original SOS study is a longitudinal non-randomized controlled study aiming to assess the effect of bariatric surgery on obesity-related mortality and morbidity. Participants included in the present report had adiponectin measurement available at baseline and no prevalent RA. The diagnosis of RA was retrieved through the Swedish National Patient Register. Results During a follow-up for up to 29 years, 82 study participants developed RA. Elevated baseline adiponectin levels were associated with a higher risk of developing RA independently of other factors, including C-reactive protein (CRP) and smoking [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.12-2.60 for an increase in adiponectin of 10 mg/L, p = 0.01]. After stratifying the population according to adiponectin and CRP median at baseline, study participants with both adiponectin and CRP above the median had a higher risk of developing RA compared to subjects with adiponectin and CRP below the median (HR 2.80, 95% CI 1.25-6.31, p = 0.01). Conclusions In this cohort of subjects with obesity followed up for up to 29 years, high serum adiponectin levels at baseline were associated with an increased risk for RA. Moreover, subjects with both high adiponectin and CRP levels at baseline were at particular risk of developing RA. ClinicalTrials.gov Identifier: NCT01479452.
32471455 TDAG8 deficiency reduces satellite glial number and pro-inflammatory macrophage number to 2020 May 29 BACKGROUND: The autoimmune disease rheumatoid arthritis (RA) affects approximately 1% of the global population. RA is characterized with chronic joint inflammation and often associated with chronic pain. The imbalance of pro-inflammatory and anti-inflammatory macrophages is a feature of RA progression. Glial cells affecting neuronal sensitivity at both peripheral and central levels may also be important for RA progression and associated pain. Genetic variants in the T cell death-associated gene 8 (TDAG8) locus are found to associate with spondyloarthritis. TDAG8 was also found involved in RA disease progression and associated hyperalgesia in the RA mouse model. However, its modulation in RA remains unclear. METHODS: To address this question, we intra-articularly injected complete Freund's adjuvant (CFA) into TDAG8(+/+), TDAG8(-/-) or wild-type mice, followed by pain behavioral tests. Joints and dorsal root ganglia were taken, sectioned, and stained with antibodies to observe the number of immune cells, macrophages, and satellite glial cells (SGCs). For compound treatments, compounds were intraperitoneally or orally administered weekly for 9 consecutive weeks after CFA injection. RESULTS: We demonstrated that TDAG8 deletion slightly reduced RA pain in the early phase but dramatically attenuated RA progression and pain in the chronic phase (> 7 weeks). TDAG8 deletion inhibited an increase in SGC number and inhibition of SGC function attenuated chronic phase of RA pain, so TDAG8 could regulate SGC number to control chronic pain. TDAG8 deletion also reduced M1 pro-inflammatory macrophage number at 12 weeks, contributing to the attenuation of chronic RA pain. Such results were further confirmed by using salicylanilide derivatives, CCL-2d or LCC-09, to suppress TDAG8 expression and function. CONCLUSIONS: This study demonstrates that TDAG8 deletion reduced SGC and M1 macrophage number to relieve RA disease severity and associated chronic pain. M1 macrophages are critical for the development and maintenance of RA disease and pain, but glial activation is also required for the chronic phase of RA pain.
32189595 Liver Fibrosis in Rheumatoid Arthritis Patients Treated with Methotrexate. 2020 INTRODUCTION: Methotrexate (MTX) is a highly effective therapy for patients with rheumatoid arthritis (RA). However, it has been associated with a range of liver related adverse events. The aim of our study was to evaluate the prevalence rate of liver fibrosis in RA patients and to assess the correlation of cumulative MTX dose with hepatic fibrosis in our context. MATERIALS AND METHODS: This is a cross-sectional study, whose goal is to describe and analyze the factors correlated with the liver fibrosis in RA patients treated with methotrexate especially the cumulative dose of MTX, along the period lying between January 2012 and March 2019. The study was carried out in the Rheumatology Department of the University Hospital Hassan II of Fez. The patients have met the assessment of the ACR 2010 criteria. The data was recorded and analyzed using SPSS v20 univariate and bivariate analysis. A value of p <0.05 has been used to identify factors associated with liver fibrosis. RESULTS: A total of 319 patients with RA were recruited who were on MTX treatment. There were 276 female and 43 male patients (female: male ratio of 6.3). The average age was 53 years + /-12.4 years. The average duration of symptoms was 10.68 +/-6.9 years. RA was seropositive for the rheumatoid factor or the anti-ccp in 90.3 %. Six patients (2%) had developed liver fibrosis while on MTX therapy. In the bivariate analysis, the liver fibrosis is significantly related to the hepatic cytolysis (p<0.001) and to the combination of MTX with other DMARDs (p<0.05). However, the multiple logistic regression analysis did not find any significant association between the groups. CONCLUSION: In our context, the prevalence rate of hepatic fibrosis in patients with rheumatoid arthritis under methotrexate is low. It is seen much more in patients treated with methotrexate in combination with other disease-modifying anti-rheumatic drugs (DMARDs). These results require confirmation in a larger number of patients.