Browse

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

ID PMID Title PublicationDate abstract
31356381 Periodontal bacteria and the rheumatoid arthritis-related antigen RA-A47: the cross-reacti 2019 Sep PURPOSE OF REVIEW: The purpose of this review is to evaluate the mechanisms that underlie the association between periodontal pathogens and rheumatoid arthritis (RA). RECENT FINDINGS: This review focuses on the cross-reactivity hypothesis as a mechanism that might contribute to explain the pathologic evolution of periodontal infections from periodontitis to RA. The scientific rationale is that immune reactions following infection by periodontal bacteria might cross-react with RA autoantigens, in this way eventually leading to autoimmunity. SUMMARY: Using the rheumatoid antigen associated with RA-A47 arthritis as an antigen model and analyzing five periodontal bacteria (eg, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola, Tannerella forsythia and Prevotella intermedia), an extremely varied pattern of peptide sharing was found. In the context of the cross-reactivity hypothesis, the data allow us to glimpse the possibility of distinguishing the periodontal bacteria capable of attacking the periodontal tissue from those that are additionally equipped with a rheumatologic potential by virtue of the sharing of peptide sequences with RA antigens.
32598670 [Rheumatoid arthritis: achievements and unresolved issues]. 2019 May 15 Success in a treatment of rheumatoid arthritis (RA), associated with a development of new medications and improving treatment strategies, allows to achieve remission in many patients. Despite this a lot of theoretical and clinical issues remain, including a definition of the term "remission", its characteristics and types as well as approaches to optimal tactics of "symptomatic" and "pathogenetic" drug therapy at different stages of the disease. Use of a such tactics will allow to induce quickly a state of remission and maintain it for a long term. Further research is needed which should be directed to investigation of a heterogeneity of RA pathogenetic mechanisms and to elaboration of approaches to its early diagnosis as well as to improving methods for monitoring a disease activity, biomarkers of efficacy and resistance to therapy, and finally, to developing of a differentiated therapy, including a search for new "therapeutic" targets.
31629903 Role of biological agents in treatment of rheumatoid arthritis. 2019 Dec Advances in understanding of the pathophysiology of rheumatoid arthritis with concurrent advances in protein engineering led to the development of biological disease-modifying antirheumatic drugs which have dramatically revolutionized the treatment of this condition. This review article focuses on the role of biological agents currently employed in the treatment of rheumatoid arthritis, as well as novel biological agents in development.
30860323 [Rheumatoid arthritis : imagery what is new ?]. 2019 Mar 6 In 2013, EULAR made a number of recommendations regarding the contribution of modern imaging : MRI and ultrasound as an aid to the diagnosis and for the monitoring of rheumatoid arthritis. This article aims to review if these recommendations are still relevant and if some questions have been resolved since then by new studies.
30729470 In Vivo Models of Rheumatoid Arthritis. 2019 Rheumatoid arthritis (RA) models in mice induced by immunization enable the analyses of molecular mechanism involved in disease development, progression, and resolution of inflammation. Here, we describe three different models mimicking clinic symptoms of human rheumatoid arthritis, which could be transferable to any genetically modified mouse. We will present the protocol for collagen-induced arthritis (CIA), K/BxN serum-induced arthritis (SIA), and the antigen-induced arthritis (AIA) models. To do so, we will detail their way of induction but also how to analyze RA clinical score and pathology characterization. Finally, we will briefly discuss the main characteristics and disadvantages of all three models.
30880357 Imaging in rheumatoid arthritis: the role of magnetic resonance imaging and computed tomog 2019 Nov In suspected and diagnosed rheumatoid arthritis (RA), magnetic resonance imaging (MRI) allows detection of all relevant pathologies, such as synovitis, tenosynovitis, bone marrow edema (osteitis), bone erosion and cartilage damage. MRI is more sensitive than clinical examination for monitoring disease activity (i.e., inflammation) and more sensitive than conventional radiography and ultrasonography for monitoring joint destruction. In suspected RA, MRI bone marrow edema predicts development of RA, and in early RA patients, it predicts subsequent structural damage progression. CT is the standard reference imaging modality for visualizing bone damage, including bone erosions in RA, but lacks sensitivity for soft-tissue changes, including synovitis and tenosynovitis. CT has a minimal role in RA clinical trials and practice, except in selected patients where MRI is contraindicated or not available or if crystal arthritis such as gout or pseudo-gout is suspected. MRI has documented utility in diagnosis, monitoring and prognostication of patients with RA and is increasingly used for these purposes in clinical practice and particularly clinical trials.
31206910 Cytokines in gingivocrevicular fluid of rheumatoid arthritis patients: A review of the lit 2019 Sep OBJECTIVE: Rheumatoid arthritis (RA) and periodontitis share several pathological features including bone and soft tissue destruction and high levels of circulating inflammatory proteins. Studies related to cytokines in the periodontal inflammatory exudate (gingivocrevicular fluid, GCF) of RA patients might provide insight into the association between periodontitis and RA. The aim of our study was to review the literature on cytokines in GCF of RA patients including the effect of anti-rheumatic treatment with biological disease-modifying anti-rheumatic drugs (DMARDs) and periodontal treatment on these cytokines. MATERIALS AND METHODS: MedLine/PubMed searches with different combinations of keywords "rheumatoid arthritis or RA" and "crevicular fluid or GCF" until June 2019 revealed 64 articles. Ten cross-sectional observational studies and nine treatment studies fulfilled the inclusion criteria. RESULTS: Rheumatoid arthritis patients have increased circulating and GCF levels of pro-inflammatory cytokines and proteins, despite anti-rheumatic treatment with biological DMARDs. Presence of periodontitis was accompanied by higher cytokine and protein levels. Treatment of periodontitis resulted in a decrease of these levels. CONCLUSION: Analysis of GCF of RA patients reveals that the relationship between periodontitis and RA is bidirectional, probably caused by a non-specific inflammatory burden. Data for a specific relationship are barely present in GCF.
31498682 Rituximab biosimilar CT-P10 for the treatment of rheumatoid arthritis. 2019 Oct Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by long-standing inflammation in multiple joints. Rituximab, a monoclonal antibody, which binds to CD20, is effective in suppressing disease activity and preventing joint damage in RA. CT-P10 was developed as a biosimilar of rituximab and approved for use to treat hematologic malignancies and immune diseases including RA. Area covered: This article describes the need for this biosimilar and summarizes the non-clinical studies verifying the physicochemical and biologic similarities and the clinical studies confirming the clinical similarity of CT-P10 to rituximab in patients with RA. Expert opinion: CT-P10 had been evaluated and proven the efficacy and safety in RA in Phase I and III randomized controlled trial with extension studies including a switching regimen. Therefore, CT-P10 is recommended in the treatment of RA.
31196644 Preventing Rheumatoid Arthritis: A Global Challenge. 2019 Jul Significant advancements have been made in the discovery of gene signatures, biomarkers, novel therapeutic targets, diagnostic tools, and risk factors that predict the development of rheumatoid arthritis (RA). There is also overwhelming evidence that treatment of early RA can prevent or alter disease progression and potentially lead to drug-free remission. Despite these advancements, there are significant challenges to identifying patients at risk of developing RA on a global scale. This commentary provides an overview of challenges related to the primary, secondary, and tertiary prevention of RA in the context of health care systems. Patient-level, provider-level, and health care system-level barriers to implementing prevention strategies are discussed. Strategies and opportunities to address these challenges, on both a local and global scale, are reported. Benefits as well as potential negative consequences that may be associated with implementation of prevention strategies for RA are discussed in the context of individuals and public health.
31407543 [THE DEVELOPMENT OF TREATMENTS IN RHEUMATOID ARTHRITIS]. 2019 Aug Rheumatology is an ancient field in medicine which deals with inflammatory diseases affecting the joints, muscles and skeleton. Rheumatic diseases challenge patients and care providers coping with chronic pain, fatigue, depression, low self-esteem and agony. The hallmark of rheumatic diseases is rheumatoid arthritis. In this review, we will present the variety of treatments that are available today. Some of them, created a revolution in the patient's prognosis and quality of life.
30878974 Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy a 2019 Jun OBJECTIVES: To unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally. METHODS: 144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression. RESULTS: Cellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) d iffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression. CONCLUSIONS: We demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.
31703281 Wnt Signaling and Biological Therapy in Rheumatoid Arthritis and Spondyloarthritis. 2019 Nov 7 The Wnt signaling pathway plays a key role in several biological processes, such as cellular proliferation and tissue regeneration, and its dysregulation is involved in the pathogenesis of many autoimmune diseases. Several evidences support its role especially in bone complications of rheumatic diseases. In Rheumatoid Arthritis (RA), the Wnt signaling is implicated in systemic and localized bone loss, while available data of its role in Spondyloarthritis (SpA) are conflicting. In the last few decades, the quality of life of rheumatic patients has been dramatically improved by biological therapy, targeting cytokines involved in the pathogenesis of these diseases like tumor necrosis factor (TNF)α, interleukin (IL)-1, IL-6, IL-17. In this review, we reviewed the role of Wnt signaling in RA and SpA, focusing on the effect of biological therapy on this pathway and its possible clinical implications.
30824879 Platelets: emerging facilitators of cellular crosstalk in rheumatoid arthritis. 2019 Apr Rheumatoid arthritis (RA) is an autoimmune disease in which a variety of circulating pro-inflammatory cells and dysregulated molecules are involved in disease aetiology and progression. Platelets are an important cellular element in the circulation that can bind several dysregulated molecules (such as collagen, thrombin and fibrinogen) that are present both in the synovium and the circulation of patients with RA. Platelets not only respond to dysregulated molecules in their environment but also transport and express their own inflammatory mediators, and serve as regulators at the boundary between haemostasis and immunity. Activated platelets also produce microparticles, which further convey signalling molecules and receptors to the synovium and circulation, thereby positioning these platelet-derived particles as strategic regulators of inflammation. These diverse functions come together to make platelets facilitators of cellular crosstalk in RA. Thus, the receptor functions, ligand binding potential and dysregulated signalling pathways in platelets are becoming increasingly important for treatment in RA. This Review aims to highlight the role of platelets in RA and the need to closely examine platelets as health indicators when designing effective pharmaceutical targets in this disease.
31921178 PKM2: A Potential Regulator of Rheumatoid Arthritis via Glycolytic and Non-Glycolytic Path 2019 Immunometabolism provides a new perspective on the pathogenesis of rheumatoid arthritis (RA). In recent years, there have been investigations focusing on the role of intracellular glucose metabolism in the pathogenesis of RA. Previous studies have shown that glycolysis of synovial tissue is increased in RA patients, while glycolysis inhibitors can significantly inhibit synovitis. Pyruvate kinase (PK) is a key enzyme in glycolysis, catalyzing the final rate-limiting step in the process. An isoform of PK, PKM2, provides favorable conditions for the survival of tumor cells via its glycolytic or non-glycolytic functions and has become a potential therapeutic target in tumors. RA synovium has the characteristic of tumor-like growth, and, moreover, increased expression of PKM2 was identified in the synovial tissue of RA patients in recent studies, indicating the underlying role of PKM2 in RA. PKM2 has potential value as a new therapeutic target or biomarker for RA, but its exact role in RA remains unclear. In this review, the properties of PKM2 and existing research concerning PKM2 and RA are thoroughly reviewed and summarized, and the possible role and mechanism of PKM2 in RA are discussed.
30578544 The genetic pathogenesis, diagnosis and therapeutic insight of rheumatoid arthritis. 2019 May Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes chronic inflammation of the joints. RA is a heterogeneous disorder caused by an abnormal autoimmune response triggered by the complex interactions of genetic and environmental factors that contribute to RA etiology. However, its underlying pathogenic mechanisms are yet to be fully understood. In this review, I provide an overview of the pathogenesis, diagnosis and therapeutic insight in the clinical management of RA in light of the recent updates to classification criteria and recent discoveries of genetic loci associated with susceptibility for RA.
31333647 How Autoantibodies Regulate Osteoclast Induced Bone Loss in Rheumatoid Arthritis. 2019 Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by autoimmunity that triggers joint inflammation and tissue destruction. Traditional concepts of RA pathogenesis have strongly been focused on inflammation. However, more recent evidence suggests that autoimmunity per se modulates the disease and in particular bone destruction during the course of RA. RA-associated bone loss is caused by increased osteoclast differentiation and activity leading to rapid bone resorption. Autoimmunity in RA is based on autoantibodies such as rheumatoid factor (RF) and autoantibodies against citrullinated proteins (ACPA). These autoantibodies exert effector functions on immune cells and on bone resorbing osteoclasts, thereby facilitating bone loss. This review summarizes potential pathways involved in increased destruction of bone tissue in RA, particularly focusing on the direct and indirect actions of autoantibodies on osteoclast generation and function.
32001168 When the first visit to the rheumatologist is established rheumatoid arthritis. 2019 Oct The outlook for people living with rheumatoid arthritis (RA) has improved tremendously in a generation. Major contributions to this include recognition of the importance of early treatment initiation, improved understanding of the pathobiology, the identification of therapeutic targets and their subsequent validation in clinic trials and the realisation of the importance of 'tight control' of inflammatory responses. Despite these advances, many patients meeting classification criteria present for the first time to a rheumatologist with longstanding symptoms. There is no definition as to when RA becomes 'established'. But there is evidence that a 'window of opportunity' exists over about 12-16 weeks symptom duration, during which treatment intervention gives rise to the most optimal outcomes. This review addresses issues regarding the management of patients presenting outside the window of opportunity in terms of heterogeneity of presentation, assessment, therapeutic goals and treatment options as well as the importance of a multidisciplinary approach to holistic care.
31899021 Prevention and cure: The major unmet needs in the management of rheumatoid arthritis. 2020 Jun The outcome of treatment of patients with rheumatoid arthritis (RA) has qualitatively improved in recent years due to better and earlier treatment approaches, and new drugs. It is now generally accepted that the phenotype of RA is the end-point of a disease continuum. Large retrospective studies have identified anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor in the stored serum of patients, years before the development of clinical RA. Recent data suggest mucosal sites such as the oral mucosa (in particular the periodontium), lung and gut may be the sites where auto-immunity is initiated. The role of bacteria at these sites is reviewed. Much recent work has focussed on the role of high resolution imaging namely ultrasound and magnetic resonance imaging in identifying subclinical inflammation in at-risk individuals with early musculoskeletal symptoms (e.g. arthralgia) but without clinical synovitis. Importantly, the first musculoskeletal site involved is usually not the joint (synovium). Sub-clinical disease predicts the onset of clinical arthritis, and its timing, in symptomatic at-risk individuals. These and other predictive markers will be described. The ability to identify patients at-risk of RA before joint involvement has led to interventions aimed at preventing/delaying disease. Once arthritis occurs, rapid remission is the target of therapy. The percentage of patients with RA achieving clinical remission has improved markedly compared with a few decades ago. The optimum outcome is to induce remission sufficiently profound so that therapy can be stopped, without flare, that is drug-free remission, which is effectively cure. Limitations of the tools used to measure remission, the outcome of tapering therapy, and new approaches to achieve successful drug cessation are described. Overall, this article reviews progress towards meeting the unmet needs of prevention/cure.
31618926 Where to Stand with Stromal Cells and Chronic Synovitis in Rheumatoid Arthritis? 2019 Oct 15 The synovium exercises its main function in joint homeostasis through the secretion of factors (such as lubricin and hyaluronic acid) that are critical for the joint lubrication and function. The main synovium cell components are fibroblast-like synoviocytes, mesenchymal stromal/stem cells and macrophage-like synovial cells. In the synovium, cells of mesenchymal origin modulate local inflammation and fibrosis, and interact with different fibroblast subtypes and with resident macrophages. In pathologic conditions, such as rheumatoid arthritis, fibroblast-like synoviocytes proliferate abnormally, recruit mesenchymal stem cells from subchondral bone marrow, and influence immune cell activity through epigenetic and metabolic adaptations. The resulting synovial hyperplasia leads to secondary cartilage destruction, joint swelling, and pain. In the present review, we summarize recent findings on the molecular signature and the roles of stromal cells during synovial pannus formation and rheumatoid arthritis progression.
30837986 Humanized Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Precl 2019 Rodent models of rheumatoid arthritis (RA) have been used over decades to study the immunopathogenesis of the disease and to explore intervention strategies. Nevertheless, mouse models of RA reach their limit when it comes to testing of new therapeutic approaches such as cell-based therapies. Differences between the human and the murine immune system make it difficult to draw reliable conclusions about the success of immunotherapies. To overcome this issue, humanized mouse models have been established that mimic components of the human immune system in mice. Two main strategies have been pursued for humanization: the introduction of human transgenes such as human leukocyte antigen molecules or specific T cell receptors, and the generation of mouse/human chimera by transferring human cells or tissues into immunodeficient mice. Recently, both approaches have been combined to achieve more sophisticated humanized models of autoimmune diseases. This review discusses limitations of conventional mouse models of RA-like disease and provides a closer look into studies in humanized mice exploring their usefulness and necessity as preclinical models for testing of cell-based therapies in autoimmune diseases such as RA.