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ID PMID Title PublicationDate abstract
33512020 Rheumatoid arthritis in low-level toluene-exposed workers based on nationwide medical surv 2021 Apr BACKGROUND: There is growing evidence that exposure to organic solvents can play a role in the etiology of rheumatoid arthritis (RA). This prospective cohort study aimed to investigate the association between RA and toluene exposure. METHODS: The study cohort consisted of Korea Occupational Safety and Health Agency data from male workers exposed to toluene who had undergone a toluene-associated special medical examination at least once between January 1, 2000 and December 31, 2004 (n = 148,870). The morbidity from RA based on hospital admission records was estimated from 2000 to 2005 using National Health Insurance Claim Data. The standardized admission ratio (SAR) for RA was calculated with reference to the general population. Levels of urinary hippuric acid (HA), a metabolite of toluene, were measured and used for exposure assessment. RESULTS: Toluene-exposed workers were at an elevated risk of seropositive rheumatoid arthritis (ICD-10 code M05) with an SAR of 2.38 (95% confidence interval [CI]: 1.14-4.37) and other rheumatoid arthritis (M06) with an SAR of 1.22 (95% CI: 0.91-1.59). When data were stratified according to the duration of toluene exposure and by tertiles of urinary HA level, no significant difference was apparent. CONCLUSION: SARs of the toluene-exposed workers are higher than that of the general reference population, indicating that exposure to toluene may contribute to an increased risk of RA. Further studies of toluene-exposed workers with longer follow-up are needed.
34016483 Triggers of Cardiovascular Diseases in Rheumatoid Arthritis. 2022 Jun The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) is higher than that in patients without RA, and it is even higher than that in patients with diabetes. Autoimmune-mediated inflammation is observed in patients with RA, resulting in endothelial dysfunction, oxidative stress and activation, and vascular migration of white blood cells. Traditionally, RA-associated CVD was assumed to be mediated by disease-related inflammation, resulting in atherosclerosis (AS). However, this concept has been challenged because treatment with anti-rheumatic drugs, such as methotrexate or proinflammatory cytokine antagonists, such as tumor necrosis factor-alpha (TNF-α) inhibitors, did not reduce the risk of CVD in patients with RA. Current cardiovascular guidelines recommend screening and treatment of CVD risk factors in patients with RA but without clear biomarkers and treatment goals. There is no scientific basis for establishing therapeutic targets for cardiovascular risk factors in RA. Numerous studies have shown that the mechanism of early cardiac dysfunction in patients with RA may occur prior to AS. Therefore, it is crucial to explore the related mechanisms to prevent early cardiac dysfunction in patients with RA.
33589107 Pregnancy and Management in Women with Rheumatoid Arthritis, Systemic Lupus Erythematosus, 2021 Mar Management of women with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and obstetric antiphospholipid syndrome (APS) during pregnancy presents unique clinical challenges. Women with both RA and SLE can have disease flares during pregnancy, leading to pregnancy complications, such as preeclampsia, small-for-gestational-age infants, and preterm delivery. Disease should be under control prior to conception. Women with obstetric APS need to be anticoagulated during pregnancy. Many but not all antirheumatic medications can be used during pregnancy and lactation.
33666522 Palindromic rheumatism: a unique and enigmatic entity with a complex relationship with rhe 2021 Apr INTRODUCTION: Palindromic rheumatism (PR) is a form of relapsing/remitting arthritis that may evolve to chronic rheumatic disease, mainly rheumatoid arthritis (RA). The exact nature of PR is unclear, as it may be considered a disease in itself, an abortive form of RA or just a pre-RA stage. AREAS COVERED: The authors review the most relevant epidemiological and clinical aspects of PR, especially the pathogenetic role of autoimmunity in PR, with most patients having a characteristic autoantibody profile similar to that observed in RA. The role of autoinflammation is also discussed. A literature review on the rate of RA progression and its prognostic factors was analyzed. Data on the efficacy of drug therapies used to treat PR are presented. PubMed was searched using the terms 'palindromic rheumatism' OR 'palindromic arthritis'. EXPERT OPINION: PR is a disease entity with a close but unclear relationship with RA. In PR there is an unmet need, which is to clarify the clinical spectrum and elucidate the risk factors for evolution to RA. The role of autoimmunity and the autoinflammatory component should be investigated. Since most patients evolve to RA, PR may display a unique therapeutic opportunity to avoid this evolution.
33001010 Therapeutic Potential of Non-Coding RNAs and TLR Signalling Pathways in Rheumatoid Arthrit 2021 BACKGROUND: Rheumatoid Arthritis (RA) is a common connective tissue disease, characteristic of chronic and invasive synovitis in single or multiple joints and vasculitis. RA is a heterogeneous disease with unclear pathogenesis. Therefore, exploring the etiology and pathogenesis of the disease is essential for identifying new promising treatment strategies for RA. Accumulated data have implicated the significant role of non-coding RNA in RA, some of which are demonstrated to regulate inflammation and autoimmunity in RA through the Toll-Like Receptor (TLR) signaling pathway. To clarify the mechanism of non-coding RNA regulating the generation of proinflammatory mediators is helpful for understanding the pathogenesis of RA. Moreover, these well established non-coding RNAs can serve as novel biotargets for RA diagnosis and treatment. CONCLUSION: Here, we summarize currently available data on non-coding RNAs, TLRs, and the underlying molecular mechanisms in RA. This review will provide insight into the potential use of noncoding RNA as disease diagnosis and treatment markers for RA.
34440629 Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheu 2021 Jul 22 Monocytes/macrophages play a central role in chronic inflammatory disorders, including rheumatoid arthritis (RA). Activation of these cells results in the production of various mediators responsible for inflammation and RA pathogenesis. On the other hand, the depletion of macrophages using specific antibodies or chemical agents can prevent their synovial tissue infiltration and subsequently attenuates inflammation. Their plasticity is a major feature that helps the switch from a pro-inflammatory phenotype (M1) to an anti-inflammatory state (M2). Therefore, understanding the precise strategy targeting pro-inflammatory monocytes/macrophages should be a powerful way of inhibiting chronic inflammation and bone erosion. In this review, we demonstrate potential consequences of different epigenetic regulations on inflammatory cytokines production by monocytes. In addition, we present unique profiles of monocytes/macrophages contributing to identification of new biomarkers of disease activity or predicting treatment response in RA. We also outline novel approaches of tuning monocytes/macrophages by biologic drugs, small molecules or by other therapeutic modalities to reduce arthritis. Finally, the importance of cellular heterogeneity of monocytes/macrophages is highlighted by single-cell technologies, which leads to the design of cell-specific therapeutic protocols for personalized medicine in RA in the future.
34073629 The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Mo 2021 May 26 Rheumatoid arthritis (RA) is a typical autoimmune-mediated rheumatic disease presenting as a chronic synovitis in the joint. The chronic synovial inflammation is characterized by hyper-vascularity and extravasation of various immune-related cells to form lymphoid aggregates where an intimate cross-talk among innate and adaptive immune cells takes place. These interactions facilitate production of abundant proinflammatory cytokines, chemokines and growth factors for the proliferation/maturation/differentiation of B lymphocytes to become plasma cells. Finally, the autoantibodies against denatured immunoglobulin G (rheumatoid factors), EB virus nuclear antigens (EBNAs) and citrullinated protein (ACPAs) are produced to trigger the development of RA. Furthermore, it is documented that gene mutations, abnormal epigenetic regulation of peptidylarginine deiminase genes 2 and 4 (PADI2 and PADI4), and thereby the induced autoantibodies against PAD2 and PAD4 are implicated in ACPA production in RA patients. The aberrant expressions of non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) in the immune system undoubtedly derange the mRNA expressions of cytokines/chemokines/growth factors. In the present review, we will discuss in detail the expression of these ncRNAs and their target molecules participating in developing RA, and the potential biomarkers for the disease, its diagnosis, cardiovascular complications and therapeutic response. Finally, we propose some prospective investigations for unraveling the conundrums of rheumatoid pathogenesis.
34543128 Sinapic Acid Attenuates Rheumatoid Arthritis Through Reducing Inflammation and Oxidative S 2021 Sep Sinapic acid (SA) was reported to protect against inflammation in various types of diseases. However, the role of SA in rheumatoid arthritis remains unclear. This study was designed to investigate the role of SA on rheumatoid arthritis. Rheumatoid arthritis mouse model was established by collagen immunization [collagen-induced arthritis (CIA)]. Histological analysis of articular cartilage tissue was carried out by hematoxylin and eosin (H&E) staining. Serum concentrations of tumor necrosis factor alpha and interleukin 6 were determined through enzyme-linked immunosorbent assay (ELISA). Oxidative damage indexes such as superoxide dismutase activity, malondialdehyde detection, glutathione detection, and catalase were determined by biochemical analysis. The protein levels of related genes were determined using Western blot. In CIA model, SA treatment attenuated paw swelling and clinical score of arthritis, attenuated articular cartilage tissues edema and infiltration of inflammatory cells, suppressed inflammatory cytokines release, and attenuated oxidative damage indexes. Mechanically, SA suppressed immune responses through inhibiting the IκB kinase (IKKs). SA attenuates rheumatoid arthritis through reducing inflammation and oxidative stress by downregulating IKKs.
34484118 Graves' Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study. 2021 BACKGROUND: The frequent coexistence of Graves' disease (GD) and rheumatoid arthritis (RA) has been cited and discussed in observational studies, but it remains a question as to whether there is a causal effect between the two diseases. METHODS: We retrieved genome-wide association study (GWAS) summary data of GD and RA from BioBank Japan (BBJ). Single nucleotide polymorphisms (SNPs) associated with diseases of interest were selected as instrumental variables (IVs) at a genome-wide significance level (P < 5.0 × 10(-8)). The random-effects inverse variance weighted method (IVW) was used to combine the causal effect of IVs. The horizontal pleiotropy effect was analyzed by MR-Egger and weighted median method sensitivity test. A leave-one-out analysis was conducted to avoid bias caused by a single SNP. The statistical power of our MR result was calculated according to Brion's method. RESULTS: Our study discovered a bidirectional causal effect between GD and RA. The presence of RA may increase the risk of GD by 39% (OR 1.39, 95% CI 1.10-1.75, P = 0.007). Similarly, the existence of GD may increase the risk of RA by 30% (OR 1.30, 95% CI 0.94-1.80, P = 0.112). Our study provides 100% power to detect the causal effect of RA on GD risk, and vice versa. CONCLUSIONS: We found a bidirectional causal effect between GD and RA in an Asian population. Our study supported the clinical need for screening GD in RA patients, and vice versa. The potential benefit of sound management of RA in GD patients (or GD in RA patients) merits excellent attention. Moreover, novel satisfactory medicine for RA may be applicable to GD and such potential is worthy of further investigation.
33491519 Rheumatoid arthritis relapse in patients with other iatrogenic immunodeficiency-associated 2021 Nov OBJECTIVES: Rheumatoid arthritis (RA) in patients undergoing immunosuppressive therapy (IS) is sometimes involved with other iatrogenic immunodeficiency-associated lymphoproliferative disorders (LPD). We aimed to clarify the effects of LPD treatment on RA and the current status of RA treatment options after LPD onset and subsequent IS withdrawal. METHODS: We retrospectively analyzed data of patients who had RA with LPD and examined the relationship between LPD course and RA treatment as well as that between RA relapse and LPD treatment. RESULTS: LPD patients were categorized into two groups: patients who regressed spontaneously (n = 19) and those who needed chemotherapy (n = 12). The chemotherapy group had significantly less RA relapse than the spontaneous regression group (p = .041). RA almost relapsed early in the spontaneous regression group and needed treatment for RA. Chemotherapy with rituximab prevented long-term RA relapse, and RA did not relapse for long even after rituximab monotherapy. The total dose of rituximab in monotherapy correlated with the time to RA relapse. Six patients with RA relapse received biologics and had no LPD relapse for more than 1 year. CONCLUSIONS: Rituximab in chemotherapy for LPD may help prevent RA relapse with LPD. Large-scale studies are required in the future for verification.
33419426 Clinical and cost effectiveness of arthritis gloves in rheumatoid arthritis (A-GLOVES): ra 2021 Jan 8 BACKGROUND: Arthritis (or compression) gloves are widely prescribed to people with rheumatoid arthritis and other forms of hand arthritis. They are prescribed for daytime wear to reduce hand pain and improve hand function, and/or night-time wear to reduce pain, improve sleep and reduce morning stiffness. However, evidence for their effectiveness is limited. The aims of this study were to investigate the clinical and cost effectiveness of arthritis gloves compared to placebo gloves on hand pain, stiffness and function in people with rheumatoid arthritis and persistent hand pain. METHODS: A parallel randomised controlled trial, in adults (≥ 18 years) with rheumatoid or undifferentiated inflammatory arthritis at 16 National Health Service sites in the UK. Patients with persistent hand pain affecting function and/or sleep were eligible. Randomisation (1:1) was stratified by recent change (or not) in medication, using permuted blocks of random sizes. Three-quarter-finger length arthritis gloves (Isotoner®: applying 23-32 mmHg pressure) (intervention) were compared to loose-fitting placebo gloves (Jobskin® classic: providing no/minimal pressure) (control). Both gloves (considered to have similar thermal qualities) were provided by occupational therapists. Patients and outcome assessors were blinded; clinicians were not. The primary outcome was dominant hand pain on activity (0-10) at 12 weeks, analysed using linear regression and intention to treat principles. RESULTS: Two hundred six participants were randomly assigned (103 per arm) and 163 (84 intervention: 79 control) completed 12-week follow-up. Hand pain improved by 1.0 (intervention) and 1.2 (control), an adjusted mean difference of 0.10 (95% CI: - 0.47 to 0.67; p = 0.72). Adverse events were reported by 51% of intervention and 36% of control group participants; with 6 and 7% respectively, discontinuing glove wear. Provision of arthritis gloves cost £129, with no additional benefit. CONCLUSION: The trial provides evidence of no clinically important effect of arthritis gloves on any of the trial outcomes (hand pain, function and stiffness) and arthritis gloves are not cost-effective. The clinical and cost-effectiveness results support ceasing provision of arthritis gloves in routine clinical practice. FUNDING: National Institute for Health Research. TRIAL REGISTRATION: ISRCTN, ISRCTN25892131 ; Registered 05/09/2016: retrospectively registered.
33458965 Effect of mannose-binding lectin gene polymorphisms on the risk of rheumatoid arthritis: E 2021 Mar BACKGROUND: The effect of mannose-binding lectin (MBL) gene polymorphisms on susceptibility of rheumatoid arthritis (RA) were evaluated in ethnically different populations, whereas the results were always inconsistent. MATERIALS AND METHODS: Fourteen articles involving 36 datasets were recruited to evaluate the association between MBL gene polymorphisms and rheumatoid arthritis in a meta-analysis. The random or fixed effect models were used to evaluate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: Stratified analysis by ethnicities was conducted and the result revealed that rs1800450 (T vs C, OR = 1.32, 95% CI: 1.04-1.67, P < .05) and MBL-A/O (T vs C, OR = 1.20, 95% CI: 1.08-1.34, P < .001) were strongly associated with RA in Brazilian populations. In addition, the significant relationship between rs11003125 (T vs C, OR = 1.16, 95% CI: 1.06-1.26, P < .05) with RA were also observed in East Asian populations. Meanwhile, the inverse associations between rs5030737 with RA in East Asians and rs1800450 with RA in Indians were acquired. However, no association between any MBL polymorphism with RA susceptibility was confirmed in Caucasians. CONCLUSIONS: The structural polymorphisms in exon 1 of MBL gene may significantly contribute to susceptibility and development of RA in Brazilian and Indian populations, whereas the functional polymorphisms in the promoter region were more likely to associate with RA in East Asians.
33453247 Role of CCL2/CCR2 axis in the immunopathogenesis of rheumatoid arthritis: Latest evidence 2021 Mar 15 Evidence suggests that uncontrolled immune system responses and their components play a significant role in developing rheumatoid arthritis (RA), which is considered an autoimmune disease (AD). Among immune system mediators, cytokines and chemokines are involved in numerous physiological and pathological processes. CCL2 or monocyte chemoattractant protein-1 (MCP-1) is known as a CC chemokine that can induce the locomotion and recruitment of monocytes and macrophages to the site of injury. When CCL2 binds to its receptors, the most important of which is CCR2, various signaling pathways are triggered, eventually leading to various immunological events such as inflammation. This chemokine also participates in several events involved in RA pathogenesis, such as osteoclastogenesis, migration of effector T cells to the RA synovium tissue, and angiogenesis. In this review article, the role of the CCL2/CCR2 axis in RA pathogenesis and the immunotherapy opportunities based on CCL2/CCR2 axis targeting has been discussed based on existing investigations.
33746606 Perspectives on long pentraxin 3 and rheumatoid arthritis: several potential breakthrough 2021 Rheumatoid arthritis (RA) is a systemic chronic autoimmune inflammatory disease which is mainly characterized by synovitis and results in a severe burden for both the individual and society. To date, the underlying mechanisms of RA are still poorly understood. Pentraxin 3 (PTX3) is a typical long pentraxin protein which has been highly conserved during evolution. Meanwhile, functions as well as properties of PTX3 have been extensively studied. Several studies identified that PTX3 plays a predominate role in infection, inflammation, immunity and tumor. Interestingly, PTX3 has also been verified to be closely associated with development of RA. We therefore accomplished an elaboration of the relationships between PTX3 and RA. Herein, we mainly focus on the associated cell types and cognate cytokines involved in RA, in combination with PTX3. This review infers the insight into the interaction of PTX3 in RA and aims to provide novel clues for potential therapeutic target of RA in clinic.
34186192 Liver X receptors conserve the therapeutic target potential for the treatment of rheumatoi 2021 Aug Rheumatoid arthritis (RA) is a chronic multi-system autoimmune disease with extremely complex pathogenesis. Significantly altered lipid paradox related to the inflammatory burden is reported in RA patients, inducing 50% higher cardiovascular risks. Recent studies have also demonstrated that lipid metabolism can regulate many functions of immune cells in which metabolic pathways have altered. The nuclear liver X receptors (LXRs), including LXRα and LXRβ, play a central role in regulating lipid homeostasis and inflammatory responses. Undoubtedly, LXRs have been considered as an attractive therapeutic target for the treatment of RA. However, there are some contradictory effects of LXRs agonists observed in previous animal studies where both pro-inflammatory role and anti-inflammatory role were revealed for LXRs activation in RA. Therefore, in addition to updating the knowledge of LXRs as the prominent regulators of lipid homeostasis, the purpose of this review is to summarize the effects of LXRs agonists in RA-associated immune cells, to explore the underlying reasons for the contradictory therapeutic effects of LXRs agonists observed in RA animal models, and to discuss future strategy for the treatment of RA with LXRs modulators.
33313832 A reconciling hypothesis centred on brain-derived neurotrophic factor to explain neuropsyc 2021 Apr 6 Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease characterized by synovitis leading to joint destruction, pain and disability. Despite efficient antirheumatic drugs, neuropsychiatric troubles including depression and cognitive dysfunction are common in RA but the underlying mechanisms are unclear. However, converging evidence strongly suggests that deficit in brain-derived neurotrophic factor (BDNF) signalling contributes to impaired cognition and depression. Therefore, this review summarizes the current knowledge on BDNF in RA, proposes possible mechanisms linking RA and brain BDNF deficiency including neuroinflammation, cerebral endothelial dysfunction and sedentary behaviour, and discusses neuromuscular electrical stimulation as an attractive therapeutic option.
34139344 Animal models to study pathogenesis and treatments of cardiac disorders in rheumatoid arth 2021 Aug Although cardiac diseases such as acute myocardial infarction, heart failure and arrhythmias are the leading cause of cardiovascular complications in rheumatoid arthritis (RA), their pathogenesis is far from being understood and optimal therapeutic options to treat specifically these disorders in RA are lacking. Preclinical studies on animal models of arthritis can help to decipher the complex link between arthritis and the heart, and to identify critical pathways and novel therapeutic targets. This review presented the available data on cardiac disorders in animal models of RA, as well as the current knowledge on pathophysiology and pharmacology of these disorders. Future directions for translational studies in a cardiorheumatic perspective are proposed.
34502442 Title Current Status of the Search for Biomarkers for Optimal Therapeutic Drug Selection f 2021 Sep 2 Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive synovitis. It is significantly associated with disability, impaired quality of life, and premature mortality. Recently, the development of biological agents (including tumor necrosis factor-α and interleukin-6 receptor inhibitors) and Janus kinase inhibitors have advanced the treatment of RA; however, it is still difficult to predict which drug will be effective for each patient. To break away from the current therapeutic approaches that could be described as a "lottery," there is an urgent need to establish biomarkers that stratify patients in terms of expected therapeutic responsiveness. This review deals with recent progress from multi-faceted analyses of the synovial tissue in RA, which is now bringing new insights into diverse features at both the cellular and molecular levels and their potential links with particular clinical phenotypes.
32712721 Troublesome friends within us: the role of gut microbiota on rheumatoid arthritis etiopath 2021 Feb The role of gut microbiota on immune regulation and the development of autoimmune diseases such as rheumatoid arthritis (RA) is an emerging research topic. Multiple studies have demonstrated alterations on gut microbiota composition and/or function (referred to as dysbiosis) both in early and established RA patients. Still, research delineating the molecular mechanisms by which gut microorganisms induce the loss of immune tolerance or contribute to disease progression is scarce. Available data indicate that gut microbiota alterations are involved in RA autoimmune response by several mechanisms including the post-translational modification of host proteins, molecular mimicry between bacterial and host epitopes, activation of immune system and polarization toward inflammatory phenotypes, as well as induction of intestinal permeability. Therefore, in this review we analyze recent clinical and molecular evidence linking gut microbiota with the etiopathogenesis of RA. The potential of the gut microbiota as a diagnostic or severity biomarker is discussed, as well as the opportunity areas for the development of complementary therapeutic strategies based on the modulation of gut microbiota in the rheumatic patient.
33906448 [CME Rheumatology 23: Rheumatoid Arthritis Following COVID-19/SARS-CoV-2 Infection]. 2021 Apr CME Rheumatology 23: Rheumatoid Arthritis Following COVID-19/SARS-CoV-2 Infection Abstract. Individuals with rheumatic diseases, especially those on immuno-modulating treatment, have an increased risk of infection. On the other hand, it is known that viral infections may be a cause for acute arthralgias and of arthritis. We present in the following a case of ACPA-positive and RF-positive rheumatoid arthritis after an acute COVID-19/SARS-CoV-2 infection and discuss the possible association with the infection.