Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 35087527 | LncRNAs and Rheumatoid Arthritis: From Identifying Mechanisms to Clinical Investigation. | 2021 | Rheumatoid arthritis (RA) is a systemic chronic autoinflammatory disease, and the synovial hyperplasia, pannus formation, articular cartilage damage and bone matrix destruction caused by immune system abnormalities are the main features of RA. The use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) has achieved great advances in the therapy of RA. Yet there are still patients facing the problem of poor response to drug therapy or drug intolerance. Current therapy methods can only moderate RA progress, but cannot stop or reverse the damage it has caused. Recent studies have reported that there are a variety of long non-coding RNAs (LncRNAs) that have been implicated in mediating many aspects of RA. Understanding the mechanism of LncRNAs in RA is therefore critical for the development of new therapy strategies and prevention strategies. In this review, we systematically elucidate the biological roles and mechanisms of action of LncRNAs and their mechanisms of action in RA. Additionally, we also highlight the potential value of LncRNAs in the clinical diagnosis and therapy of RA. | |
| 35383493 | Arthritis and dentistry. | 2022 Mar | Arthritis is a common condition affecting millions of people in the UK and worldwide. All members of the dental team will be seeing and treating patients with this condition, and it is important to understand the disease, its management and medications used. This article outlines the five most common types of arthritis: osteoarthritis (OA), rheumatoid arthritis (RA), axial spondyloarthritis (sPA), juvenile idiopathic arthritis (JIA), and gout. It further discusses the medications used to treat these conditions and any dental implications. Finally, advice is offered on considerations for the dental team when treating such patients. | |
| 34713333 | [Polyarticular juvenile idiopathic arthritis and rheumatoid arthritis : Common features an | 2022 Feb | The spectrum of polyarthritic diseases in childhood as well as in adulthood is wide. In the differential diagnostics different age-related diseases must be taken into consideration. Although, a clear similarity is obvious in all age groups for the classical diseases of polyarticular juvenile idiopathic arthritis and rheumatoid arthritis with respect to the pathogenesis, clinical manifestation and treatment options, this review points to specific differences. The prognosis of polyarthritis in children mainly depends on the joint manifestation, whereas extra-articular comorbidities play a predominant role in the older adult population. | |
| 35256364 | Monarticular rheumatoid arthritis of the elbow. | 2022 Mar 7 | Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by symmetric inflammatory polyarthritis. However, RA limited to a single joint is extremely rare. Here, we report a middle-aged woman who presented with insidious right elbow arthritis. She had no other peripheral joint pain, tenderness or swelling. She had high-positive anti-cyclic citrullinated peptide antibodies. An MRI of the right elbow showed capsular distension, joint effusion and bone marrow oedema. Synovial biopsy revealed hyperplasia with lymphoplasmacytic infiltrate consistent with RA. Therapy with methotrexate 7.5 mg orally weekly was effective to control her inflammatory arthritis. This case highlights the relevance of synovial tissue analysis for patients presenting with chronic inflammatory monarthritis when the cause is not clinically evident, and the importance of considering RA even in the absence of polyarticular involvement. Delayed diagnosis and treatment of inflammatory monarthritis can lead to joint destruction and disability. | |
| 34523821 | Myocardial Dysfunction and Heart Failure in Rheumatoid Arthritis. | 2022 Feb | Rheumatoid arthritis (RA) patients have almost twice the risk of heart failure (HF) as individuals without RA, even with adjustment for the presence of ischemic heart disease. Moreover, RA patients remain at a 2-fold higher risk of mortality from HF compared to non-RA patients. These observations suggest that RA-specific inflammatory pathways are significant contributors to this increased risk of HF. Herein we summarize the epidemiology of HF in RA patients, the differences in myocardial structure or function between RA patients and non-RA patients without clinical signs of HF, and data on the role of systemic and local inflammation in RA HF pathophysiology. We also discuss the impact of subduing inflammation through the use of RA disease-modifying therapies on HF and myocardial structure and function, emphasizing gaps in the literature and areas needing further research. | |
| 35058928 | Interleukin 27 Signaling in Rheumatoid Arthritis Patients: Good or Evil? | 2021 | The occurrence and development of rheumatoid arthritis (RA) is regulated by numerous cytokines. Interleukin 27 (IL-27) is a soluble cytokine that exerts biological effects by regulating the Janus tyrosine kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway via the IL-27 receptor. IL-27 is known for its pleiotropic roles in modulating inflammatory responses. Previous studies found that IL-27 levels are elevated in RA blood, synovial fluid, and rheumatoid nodules. Cellular and animal experiments indicated that IL-27 exerts multiple regulatory functions in RA patients via different mechanisms. IL-27 inhibits ectopic-like structure (ELS) formation and CD4(+) T helper type 2 (Th2) cell, CD4(+) T helper type 17 (Th17) cell, and osteoclast differentiation in RA, contributing to alleviating RA. However, IL-27 promotes Th1 cell differentiation, which may exacerbate RA synovitis. Moreover, IL-27 also acts on RA synovial fibroblasts (RA-FLSs) and regulatory T cells (Tregs), but some of its functions are unclear. There is currently insufficient evidence to determine whether IL-27 promotes or relieves RA. Targeting IL-27 signaling in RA treatment should be deliberate based on current knowledge. | |
| 35364736 | Elucidating the role of hypoxia-inducible factor in rheumatoid arthritis. | 2022 Jun | Rheumatoid arthritis (RA) is a chronic multifactorial disease, provocative, and degenerative autoimmune condition that impacts millions of individuals around the globe. As a result of this understanding, anti-inflammatory drugs have been created, perhaps widely effective (like steroids) and highly specialized methods (including anti-TNF antibody) using biological therapies (including TNF inhibitors). Despite this, the connections between inflammatory response, articular development, and intracellular responsiveness to changes in oxygen concentration are undervalued in rheumatoid arthritis. Hypoxia, or a lack of oxygen, is thought to cause enhanced synovial angiogenesis in RA, which is mediated by some of the hypoxia-inducible factors like vascular endothelial growth factor (VEGF). Substantial genetic alterations occur when the HIF regulatory factors signaling cycle is activated, allowing organelles, tissues, and species to acclimatize to decreasing oxygen saturation. The most well-characterized hypoxia-responsive transcripts are the angiogenic stimulant VEGF, whose production is greatly elevated by hypoxia in several types of cells, especially RA synovium fibroblasts. Blocking vascular endothelial growth factors has been demonstrated to be helpful in murine models of rheumatism, indicating how hypoxia could trigger the angiogenesis process, resulting in the progression of RA. These mechanisms highlight the intimate affiliation amongst hypoxia, angiogenesis, and inflammation in rheumatoid arthritis. This review will look at how hypoxia activates molecular pathways and how other pathways involving inflammatory signals develop and sustain synovitis in rheumatoid arthritis. | |
| 35297366 | Update on the role of extracellular vesicles in rheumatoid arthritis. | 2022 Mar 17 | Rheumatoid arthritis (RA) is a heterogeneous autoimmune disorder that leads to severe joint deformities, negatively affecting the patient's quality of life. Extracellular vesicles (EVs), which include exosomes and ectosomes, act as intercellular communication mediators in several physiological and pathological processes in various diseases including RA. In contrast, EVs secreted by mesenchymal stem cells perform an immunomodulatory function and stimulate cartilage repair, showing promising therapeutic results in animal models of RA. EVs from other sources, including dendritic cells, neutrophils and myeloid-derived suppressor cells, also influence the biological function of immune and joint cells. This review describes the role of EVs in the pathogenesis of RA and presents evidence supporting future studies on the therapeutic potential of EVs from different sources. This information will contribute to a better understanding of RA development, as well as a starting point for exploring cell-free-based therapies for RA. | |
| 35118863 | Nucleic Acids for Potential Treatment of Rheumatoid Arthritis. | 2022 May 16 | Rheumatoid arthritis (RA) is a common systemic inflammatory autoimmune disease that severely affects the life quality of patients. Current therapeutics in clinic mainly focus on alleviating the development of RA or relieving the pain of patients. The emerging biological disease-modifying antirheumatic drugs (DMARDs) require long-term treatment to achieve the expected efficacy. With the development of bionanotechnology, nucleic acids fulfill characters as therapeutics or nanocarriers and can therefore be alternatives to combat RA. This review summarizes the therapeutic RNAs developed through RNA interference (RNAi), nucleic acid aptamers, DNA nanostructures-based drug delivery systems, and nucleic acid vaccines for the applications in RA therapy and diagnosis. Furthermore, prospects of nucleic acids for RA therapy are intensively discussed as well. | |
| 35401568 | MicroRNA-Mediated Epigenetic Regulation of Rheumatoid Arthritis Susceptibility and Pathoge | 2022 | MicroRNAs (miRNAs) play crucial roles in regulating the transcriptome and development of rheumatoid arthritis (RA). Currently, a comprehensive map illustrating how miRNAs regulate transcripts, pathways, immune system differentiation, and their interactions with terminal cells such as fibroblast-like synoviocytes (FLS), immune-cells, osteoblasts, and osteoclasts are still laking. In this review, we summarize the roles of miRNAs in the susceptibility, pathogenesis, diagnosis, therapeutic intervention, and prognosis of RA. Numerous miRNAs are abnormally expressed in cells involved in RA and regulate target genes and pathways, including NF-κB, Fas-FasL, JAK-STAT, and mTOR pathways. We outline how functional genetic variants of miR-499 and miR-146a partly explain susceptibility to RA. By regulating gene expression, miRNAs affect T cell differentiation into diverse cell types, including Th17 and Treg cells, thus constituting promising gene therapy targets to modulate the immune system in RA. We summarize the diagnostic and prognostic potential of blood-circulating and cell-free miRNAs, highlighting the opportunity to combine these miRNAs with antibodies to cyclic citrullinated peptide (ACCP) to allow accurate diagnosis and prognosis, particularly for seronegative patients. Furthermore, we review the evidence implicating miRNAs as promising biomarkers of efficiency and response of, and resistance to, disease-modifying anti-rheumatic drugs and immunotherapy. Finally, we discuss the autotherapeutic effect of miRNA intervention as a step toward the development of miRNA-based anti-RA drugs. Collectively, the current evidence supports miRNAs as interesting targets to better understand the pathogenetic mechanisms of RA and design more efficient therapeutic interventions. | |
| 35262966 | Pros and cons of causative association between periodontitis and rheumatoid arthritis. | 2022 Jun | Research in recent decades has brought significant advancements in understanding of the molecular basis of the etiology of autoimmune diseases, including rheumatoid arthritis, a common systemic disease in which an inappropriate or inadequate immune response to environmental challenges leads to joint destruction. Recent studies have indicated that the classical viewpoint of the immunological processes underpinning the pathobiology of rheumatoid arthritis is restricted and needs to be expanded to include a more holistic and interdisciplinary approach incorporating bacteria-induced inflammatory reactions as an important pathway in rheumatoid arthritis etiology. Here, we discuss in detail data showing the clinical and molecular association of rheumatoid arthritis development with periodontal diseases. We also describe the unique role of periopathogens, which have been proposed to be crucial in the initiation and progression of this autoimmune pathological disorder. | |
| 34791359 | Treatment strategies for elderly-onset rheumatoid arthritis in the new era. | 2022 Apr 18 | Elderly-onset rheumatoid arthritis (EORA) is characterized by acute onset and clinical features of high disease activity. Anti-cyclic citrullinated peptide antibody (ACPA) positivity or the presence of bone erosions predicts a radiological joint destruction of EORA, but ACPA-negative EORA with a polymyalgia rheumatica (PMR) phenotype may also present. Biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors were beneficial both in older and in younger patients in terms of risk-benefit balance. Implementation of a treat-to-target strategy could improve EORA outcomes, but older patients have more age-related comorbidities and interstitial lung disease than younger patients. Baseline comorbidities, more frequent methotrexate dose-dependent adverse events, serious infections, cardiovascular disease events, and malignancy all influence the choice of treatment and the treatment goals for older patients. Based on articles reviewed here, it is suggested that current treatment strategies for younger patients are also useful for ACPA-positive EORA and for ACPA-negative EORA with bone erosion. Differential diagnosis of ACPA-negative EORA without erosive arthritis and PMR with peripheral manifestations is challenging, and the treatment strategy of patients presenting with this overlap phenotype remained unclear. An appropriate treatment strategy for all patients with EORA still needs to be developed. | |
| 34876670 | Acute exacerbation of interstitial lung disease associated with rheumatic disease. | 2022 Feb | Interstitial lung disease (ILD) is a cause of morbidity and mortality in patients with rheumatic diseases, such as connective-tissue diseases, rheumatoid arthritis and systemic vasculitis. Some patients with ILD secondary to rheumatic disease (RD-ILD) experience acute exacerbations, with sudden ILD progression and high mortality during or immediately after the exacerbation, and a very low 1-year survival rate. In the ILD subtype idiopathic pulmonary fibrosis (IPF), an acute exacerbation is defined as acute worsening or development of dyspnoea associated with new bilateral ground-glass opacities and/or consolidations at high-resolution CT, superimposed on a background pattern consistent with fibrosing ILD. However, acute exacerbation in RD-ILD (AE-RD-ILD) currently has no specific definition. The aetiology and pathogenesis of AE-RD-ILD remain unclear, but distinct triggers might include infection, mechanical stress, microaspiration and DMARD treatment. At this time, no effective evidence-based therapeutic strategies for AE-RD-ILD are available. In clinical practice, AE-RD-ILD is often empirically treated with high-dose systemic steroids and antibiotics, with or without immunosuppressive drugs. In this Review, we summarize the clinical features, diagnosis, management and prognosis of AE-RD-ILD, enabling the similarities and differences with acute exacerbation in IPF to be critically assessed. | |
| 34787822 | Value of Remission in Patients with Rheumatoid Arthritis: A Targeted Review. | 2022 Jan | The treat-to-target strategy, which defines clinical remission as the primary therapeutic goal for rheumatoid arthritis (RA), is a widely recommended treatment approach in clinical guidelines. Achieving remission has been associated with improved clinical outcomes, quality of life, and productivity. These benefits are likely to translate to reduced economic burden in terms of lower healthcare costs and resource utilization. As such, a literature review was conducted to better understand the economic value of remission. Despite the large heterogeneity found in RA-related economic outcomes across studies, patients in remission consistently had lower direct medical and indirect costs, less healthcare resource utilization, and greater productivity compared to those without remission. Remission was associated with 19-52% savings in direct medical costs and 37-75% savings in indirect costs. The economic value of remission should thus be considered in economic analyses of RA therapies to inform treatment and reimbursement decisions. | |
| 34825948 | [Use of biosimilars in the treatment of rheumatoid arthritis : An overview]. | 2022 Mar | Biologics have been an integral part of the treatment of rheumatoid arthritis for approximately 20 years. As patents for pharmaceuticals generally expire after 10 years, in recent years biosimilars have come onto the market. Many studies have shown that they are an equivalent alternative to the reference drug with comparable safety and efficacy. In some cases, they even showed lower rates of adverse drug reactions compared to the reference drugs. Furthermore, considerable costs can be saved by biosimilars, which amount to an annual three-digit million sum in Germany alone. Large regional differences in the prescription frequency of biosimilars in Germany can be identified, which are also reflected in the savings potential. A switch to a biosimilar is possible and desirable with the involvement of the patient. In this sense, the initial prescription of a biosimilar instead of the reference drug is also to be advocated. | |
| 34285049 | Determining in which pre-arthritis stage HLA-shared epitope alleles and smoking exert thei | 2022 Jan | OBJECTIVES: The human leukocyte antigen-shared epitope (HLA-SE) alleles and smoking are the most prominent genetic and environmental risk factors for rheumatoid arthritis (RA). However, at which pre-arthritis stage (asymptomatic/symptomatic) they exert their effect is unknown. We aimed to determine whether HLA-SE and smoking are involved in the onset of autoantibody positivity, symptoms (clinically suspect arthralgia (CSA)) and/or progression to clinical arthritis. METHODS: We performed meta-analyses on results from the literature on associations of HLA-SE and smoking with anti-citrullinated protein antibodies (ACPAs) in the asymptomatic population. Next, we studied associations of HLA-SE and smoking with autoantibody positivity at CSA onset and with progression to clinical inflammatory arthritis (IA) during follow-up. Associations in ACPA-positive patients with CSA were validated in meta-analyses with other arthralgia cohorts. Analyses were repeated for rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and anti-acetylated protein antibodies (AAPA). RESULTS: Meta-analyses showed that HLA-SE is not associated with ACPA positivity in the asymptomatic population (OR 1.06 (95% CI:0.69 to 1.64)), whereas smoking was associated (OR 1.37 (95% CI: 1.15 to 1.63)). At CSA onset, both HLA-SE and smoking associated with ACPA positivity (OR 2.08 (95% CI: 1.24 to 3.49), OR 2.41 (95% CI: 1.31 to 4.43)). During follow-up, HLA-SE associated with IA development (HR 1.86 (95% CI: 1.23 to 2.82)), in contrast to smoking. This was confirmed in meta-analyses in ACPA-positive arthralgia (HR 1.52 (95% CI: 1.08 to 2.15)). HLA-SE and smoking were not associated with RF, anti-CarP or AAPA-positivity at CSA onset. Longitudinally, AAPA associated with IA development independent from ACPA and RF (HR 1.79 (95% CI: 1.02 to 3.16)), anti-CarP did not. CONCLUSIONS: HLA-SE and smoking act at different stages: smoking confers risk for ACPA and symptom development, whereas HLA-SE mediates symptom and IA development. These data enhance the understanding of the timing of the key risk factors in the development of RA. | |
| 35398172 | Emerging nanotherapeutics alleviating rheumatoid arthritis by readjusting the seeds and so | 2022 May | Rheumatoid arthritis (RA) is a complicated autoimmune disease that results in severe joint inflammation, synovial hyperplasia, pannus formation, cartilage and bone destruction, and other RA-associated complications. Although the pathogenesis of RA remains unclear, increasing reports have shown that inflammation-relevant cells and the microenvironment of inflamed joints play a critical role in the formation and aggravation of RA. Recently, numerous nanotherapeutics have been engineered to overcome these intractable challenges by readjusting inflammation-related seeds (endothelial cells, macrophages, neutrophils, antigen-presenting cells, fibroblasts, osteoclasts, T cells, B cells, and chondrocytes) and inflamed soils (NO, cell-free DNA, hypoxia, ROS, and pro-inflammatory cytokines). In this review, we first present a detailed pathogenesis of RA, with an emphasis on the emerging advances in regulating seeds or remodeling soils for RA treatment. We then outline these intelligent therapeutics via synergistic seed-soil adjustment, particularly for spatiotemporally cascade-responsive or all-in-one integrational nanosystems. Finally, we briefly discuss the ongoing challenges and prospects for the clinical development and translation of seed soil-based therapies. | |
| 35113729 | IL-6 Revisited: From Rheumatoid Arthritis to CAR T Cell Therapy and COVID-19. | 2022 Apr 26 | The diverse biological activity of interleukin-6 (IL-6) contributes to the maintenance of homeostasis. Emergent infection or tissue injury induces rapid production of IL-6 and activates host defense through augmentation of acute-phase proteins and immune responses. However, excessive IL-6 production and uncontrolled IL-6 receptor signaling are critical to pathogenesis. Over the years, therapeutic agents targeting IL-6 signaling, such as tocilizumab, a humanized anti-IL-6 receptor antibody, have shown remarkable efficacy for rheumatoid arthritis, Castleman disease, and juvenile idiopathic arthritis, and their efficacy in other diseases is continually being reported. Emerging evidence has demonstrated the benefit of tocilizumab for several types of acute inflammatory diseases, including cytokine storms induced by chimeric antigen receptor T cell therapy and coronavirus disease 2019 (COVID-19). Here, we refocus attention on the biology of IL-6 and summarize the distinct pathological roles of IL-6 signaling in several acute and chronic inflammatory diseases. | |
| 35185910 | Folate Receptor Beta for Macrophage Imaging in Rheumatoid Arthritis. | 2022 | Non-invasive imaging modalities constitute an increasingly important tool in diagnostic and therapy response monitoring of patients with autoimmune diseases, including rheumatoid arthritis (RA). In particular, macrophage imaging with positron emission tomography (PET) using novel radiotracers based on differential expression of plasma membrane proteins and functioning of cellular processes may be suited for this. Over the past decade, selective expression of folate receptor β (FRβ), a glycosylphosphatidylinositol-anchored plasma membrane protein, on myeloid cells has emerged as an attractive target for macrophage imaging by exploiting the high binding affinity of folate-based PET tracers. This work discusses molecular, biochemical and functional properties of FRβ, describes the preclinical development of a folate-PET tracer and the evaluation of this tracer in a translational model of arthritis for diagnostics and therapy-response monitoring, and finally the first clinical application of the folate-PET tracer in RA patients with active disease. Consequently, folate-based PET tracers hold great promise for macrophage imaging in a variety of (chronic) inflammatory (autoimmune) diseases beyond RA. | |
| 35369881 | Overlapping rheumatoid arthritis and antisynthetase syndrome with secondary Sjögren's syn | 2022 Apr 4 | BACKGROUND: Overlap syndromes account for about 25% of autoimmune diseases. They are many possible combinations of known autoimmune diseases increasingly diagnosed with the identification of of a large number of autoantibodies. In this case report, we present a patient with rare overlapping rheumatoid arthritis-antisynthetase syndrome with associated secondary Sjögren's syndrome atypically presenting without interstitial lung disease. CASE PRESENTATION: A 52-year-old Sinhalese female, a known patient with type 2 diabetes mellitus, presented with a history of symmetrical inflammatory-type polyarthritis with significant morning stiffness, proximal muscle weakness, pain, and roughening of the fingertips with associated sicca symptoms of 5 months duration. Examination revealed features of active joint inflammation, mechanic's hand, xerostomia, and left-sided breast lump. Investigations confirmed the presence of rheumatoid arthritis with strongly positive rheumatoid factor (202 U/ml) and anti-cyclic citrullinated peptide antibody (717 U/ml). Antisynthetase syndrome was also diagnosed with borderline-positive anti-aminoacyl-tRNA antibodies but without interstitial lung disease. Sjögren's syndrome was confirmed by the clinical history and histology and considered a secondary disorder. As her breast lump proved to be benign, no further interventions were done. She was started on sulfasalazine and methotrexate with steroid bridging therapy and achieved remission and had good control of the disease without any joint deformity or flare-up on 6-month clinic follow-up. DISCUSSION: Overlapping rheumatoid arthritis-antisynthetase syndrome is a very rare disease with disabling complications. Early identification of the atypical presentations of the overlap syndromes, by thorough investigations, helps physicians to prescribe proper disease-modifying antirheumatoid drugs and biological drugs. It also helps predict the prognosis of the patients before they develop complications. |