-
Frontiers in Endocrinology 2023The aim of this study was to determine causal associations between inflammatory arthritis and eye diseases (disorders of sclera, cornea, iris, and ciliary body [DSCIC]...
OBJECTIVES
The aim of this study was to determine causal associations between inflammatory arthritis and eye diseases (disorders of sclera, cornea, iris, and ciliary body [DSCIC] and disorders of choroid and retina [DCR]).
METHODS
Genome-wide association studies' summary data of rheumatoid arthritis (RA) from a large-scale meta-analysis were used to identify genetically predicted RA. UK Biobank source data predicted ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA). Furthermore, data from the FinnGen Biobank were used to identify genetically predicted eye diseases. Two-sample Mendelian randomization analysis was used to assess the causal relationship between inflammatory arthritis and eye diseases in the European population. Inverse-variance weighting (IVW) was used as the primary method, while MR-Egger, weighted median, and MR-PRESSO outlier test were used to detect heterogeneity and pleiotropy.
RESULTS
Genetically determined RA was indeed observed to have a causal effect on DSCIC (odds ratio [OR] = 1.084, = 2.353 × 10) and DCR (OR = 1.151, = 1.584 × 10). AS was causally associated with DSCIC (OR = 1.068, < 2.024 × 10). In addition, PsA was also found to have a causal association with an increased risk of 17.9% for the development of DSCIC (OR = 1.179, = 0.003). On the flip side, DSCIC increased the risk of JIA (OR = 2.276, = 0.003).
CONCLUSION
Our study provided genetic evidence for the causal associations of RA, AS, and PsA with an increased risk of DSCIC, and a causal association between RA and DCR was also identified. In addition, DSCIC greatly increased the risk of JIA.
Topics: Humans; Arthritis, Psoriatic; Arthritis, Rheumatoid; Eye Diseases; Genome-Wide Association Study; Mendelian Randomization Analysis; Retinal Diseases; Spondylitis, Ankylosing
PubMed: 37876547
DOI: 10.3389/fendo.2023.1251167 -
International Journal of Molecular... Sep 2023Epithelial-mesenchymal transition (EMT) is a complex reversible biological process characterized by the loss of epithelial features and the acquisition of mesenchymal... (Review)
Review
Epithelial-mesenchymal transition (EMT) is a complex reversible biological process characterized by the loss of epithelial features and the acquisition of mesenchymal features. EMT was initially described in developmental processes and was further associated with pathological conditions including metastatic cascade arising in neoplastic progression and organ fibrosis. Fibrosis is delineated by an excessive number of myofibroblasts, resulting in exuberant production of extracellular matrix (ECM) proteins, thereby compromising organ function and ultimately leading to its failure. It is now well acknowledged that a significant number of myofibroblasts result from the conversion of epithelial cells via EMT. Over the past two decades, evidence has accrued linking fibrosis to many chronic autoimmune and inflammatory diseases, including systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and inflammatory bowel diseases (IBD). In addition, chronic inflammatory states observed in most autoimmune and inflammatory diseases can act as a potent trigger of EMT, leading to the development of a pathological fibrotic state. In the present review, we aim to describe the current state of knowledge regarding the contribution of EMT to the pathophysiological processes of various rheumatic conditions.
Topics: Humans; Epithelial-Mesenchymal Transition; Autoimmune Diseases; Sjogren's Syndrome; Arthritis, Rheumatoid; Fibrosis; Extracellular Matrix Proteins
PubMed: 37833928
DOI: 10.3390/ijms241914481 -
International Journal of Rheumatic... Nov 2023
Topics: Humans; Arthritis, Juvenile; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic
PubMed: 37563978
DOI: 10.1111/1756-185X.14845 -
Seminars in Musculoskeletal Radiology Dec 2023Arthritis has significant adverse consequences on musculoskeletal tissues and often other organs of the body. Current methods for clinical evaluation of arthritis are... (Review)
Review
Arthritis has significant adverse consequences on musculoskeletal tissues and often other organs of the body. Current methods for clinical evaluation of arthritis are suboptimal, and biomarkers that are objective and measurable indicators for monitoring of arthritis disease activity are in critical demand. Recently, total-body positron emission tomography (PET) has been developed that can collect imaging signals synchronously from the entire body at ultra-low doses and reduced scan times. These scanners have increased signal collection efficiency that overcomes several limitations of standard PET scanners in the evaluation of arthritis, and they may potentially provide biomarkers to assess local and systemic impact of the arthritis disease process. This article reviews current results from using total-body PET in the assessment of common arthritic conditions, and it outlines future opportunities and challenges.
Topics: Humans; Positron-Emission Tomography; Arthritis; Forecasting; Biomarkers
PubMed: 37935209
DOI: 10.1055/s-0043-1775746 -
Seminars in Arthritis and Rheumatism Aug 2023Polyarthritis is commonly reported in idiopathic inflammatory myositis patients, but few studies have focused on the overlap of myositis with rheumatoid arthritis which... (Review)
Review
OBJECTIVES
Polyarthritis is commonly reported in idiopathic inflammatory myositis patients, but few studies have focused on the overlap of myositis with rheumatoid arthritis which is a difficult diagnosis in the absence of well-defined diagnostic criteria. The primary objective of this scoping review was to map the field of research to explore the potential diagnoses in patients presenting with both myositis and polyarthritis.
METHODS
Two electronic databases (MEDLINE/PubMed® and Web of Science®) were systematically searched using the terms (myositis OR 'inflammatory idiopathic myopathies') AND (polyarthritis OR 'rheumatoid arthritis') without any publication date limit.
RESULTS
Among individual records, 280 reports met inclusion criteria after full-text review. There was heterogeneity in the definition of overlap myositis as well as the characteristics of rheumatoid arthritis. In many studies, key data were lacking; rheumatoid factor status was reported in 56.8% (n=151), anti-citrullinated proteins antibodies status in 18.8% (n=50), and presence or absence of bone erosions in 45.1% (n=120) of the studies. Thirteen different diagnoses were found to associate myositis with polyarthritis: antisynthetase syndrome (29.6%, n=83), overlap myositis with rheumatoid arthritis (16.1%, n=45), drug-induced myositis (20.0%, n=56), rheumatoid myositis (7.5%, n=21), inclusion body myositis (1.8%, n=5), overlap with connective tissue disease (20.0%, n=56), and others (5.0%, n=14).
CONCLUSION
The spectrum of joint and muscle inflammatory diseases encompasses many diagnoses including primitive and secondary myositis associated with RA or arthritis mimicking RA. This review highlights the need for a consensual definition of OM with RA to better individualise this entity from the numerous differential diagnoses.
Topics: Humans; Arthritis, Rheumatoid; Autoantibodies; Muscles; Myositis; Myositis, Inclusion Body
PubMed: 37210805
DOI: 10.1016/j.semarthrit.2023.152227 -
Biomedical Journal Feb 2024Nod-like receptors (NLRs) are innate immune receptors that play a key role in sensing components from pathogens and from damaged cells or organelles. NLRs form signaling... (Review)
Review
Nod-like receptors (NLRs) are innate immune receptors that play a key role in sensing components from pathogens and from damaged cells or organelles. NLRs form signaling complexes that can lead to activation of transcription factors or effector caspases - by means of inflammasome activation -Inflammatory arthritis (IA) culminating in promoting inflammation. An increasing body of research supports the role of NLRs in driving pathogenesis of IA, a collection of diseases that include rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis, and pediatric arthritis. In this review, we briefly discuss the main drivers of IA diseases and dive into the evidence for - and against - various NLRs in driving these diseases. We also review the studies examining the use of NLR and inflammasome inhibitors as potential therapies for IA.
Topics: Humans; Child; Arthritis, Psoriatic; Inflammasomes; NLR Proteins; Arthritis, Rheumatoid; Spondylitis, Ankylosing
PubMed: 37598797
DOI: 10.1016/j.bj.2023.100655 -
International Immunopharmacology Aug 2023Extracellular matrix (ECM) is a three-dimensional network entity composed of extracellular macromolecules. ECM in synovium not only supports the structural integrity of... (Review)
Review
Extracellular matrix (ECM) is a three-dimensional network entity composed of extracellular macromolecules. ECM in synovium not only supports the structural integrity of synovium, but also plays a crucial role in regulating homeostasis and damage repair response in synovium. Obvious disorders in the composition, behavior and function of synovial ECM will lead to the occurrence and development of arthritis diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and psoriatic arthritis (PsA). Based on the importance of synovial ECM, targeted regulation of the composition and structure of ECM is considered to be an effective measure for the treatment of arthritis disease. This paper reviews the current research status of synovial ECM biology, discusses the role and mechanism of synovial ECM in physiological status and arthritis disease, and summarizes the current strategies for targeting synovial ECM to provide information for the pathogenesis, diagnosis and treatment of arthritis disease.
Topics: Humans; Arthritis, Psoriatic; Synovial Membrane; Arthritis, Rheumatoid; Gout; Extracellular Matrix; Homeostasis
PubMed: 37331300
DOI: 10.1016/j.intimp.2023.110453 -
Immunotherapy Oct 2023Janus kinase inhibitors were recently approved for treatment of axial spondyloarthritis following clinical trials demonstrating benefit for symptom control. Upadacitinib... (Review)
Review
Janus kinase inhibitors were recently approved for treatment of axial spondyloarthritis following clinical trials demonstrating benefit for symptom control. Upadacitinib treatment resulted in Assessment of SpondyloArthritis International Society 40 response improvement (defined as at least 40% improvement and an absolute improvement in global assessment of disease activity, patient assessment of back pain and other indices) in 45-52% of trial participants with axial spondyloarthritis. We review the data for efficacy and safety of upadacitinib in this patient population.
Topics: Humans; Axial Spondyloarthritis; Heterocyclic Compounds, 3-Ring; Spondylarthritis; Janus Kinase Inhibitors
PubMed: 37675498
DOI: 10.2217/imt-2023-0032 -
RMD Open Nov 2023To provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid...
OBJECTIVES
To provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) phase 2b/3 upadacitinib clinical programmes.
METHODS
Data were analysed and summarised from clinical trials of RA, PsA and AS treated with upadacitinib 15 mg once daily (QD) and 30 mg QD (as of 30 June 2021). Data from adalimumab (RA and PsA) and methotrexate (RA) arms were included as comparators. Adjudicated MACEs and VTE events were presented as exposure-adjusted rates per 100 patient-years (E/100 PY). Univariable Cox proportional hazard regression analyses assessed potential associations of risk factors for MACE and VTE.
RESULTS
In total, 4298 patients received upadacitinib 15 mg (RA n=3209, PsA n=907 and AS n=182) and 2125 patients received upadacitinib 30 mg (RA n=1204 and PsA n=921). In patients with RA and PsA, rates of MACE (0.3-0.6 E/100 PY) and VTE (0.2-0.4 E/100 PY) were similar across upadacitinib doses; in patients with AS, no MACEs and one VTE event occurred. Most patients experiencing MACEs or VTE events had two or more baseline cardiovascular risk factors. Across RA and PsA groups, rates of MACEs and VTE events were similar.
CONCLUSIONS
Rates of MACEs and VTE events with upadacitinib were consistent with previously reported data for patients receiving conventional synthetic and biologic disease-modifying anti-rheumatic drugs and comparable with active comparators adalimumab and methotrexate. Associated patient characteristics are known risk factors for MACEs and VTE events.
TRIAL REGISTRATION NUMBERS
RA (SELECT-NEXT: NCT02675426; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847; SELECT-COMPARE: NCT02629159; SELECT-EARLY: NCT02706873, SELECT-CHOICE: NCT03086343), PsA (SELECT-PsA 2: NCT03104374; SELECT-PsA 1: NCT03104400), and AS (SELECT-AXIS 1: NCT03178487).
Topics: Humans; Adalimumab; Arthritis, Psoriatic; Arthritis, Rheumatoid; Methotrexate; Spondylitis, Ankylosing; Venous Thromboembolism; Clinical Trials as Topic
PubMed: 37945286
DOI: 10.1136/rmdopen-2023-003392 -
Nature Reviews. Rheumatology Nov 2023The incidence of rheumatic diseases such as rheumatoid arthritis and osteoarthritis and injuries to articular cartilage that lead to osteochondral defects is predicted... (Review)
Review
The incidence of rheumatic diseases such as rheumatoid arthritis and osteoarthritis and injuries to articular cartilage that lead to osteochondral defects is predicted to rise as a result of population ageing and the increase in high-intensity physical activities among young and middle-aged people. Current treatments focus on the management of pain and joint functionality to improve the patient's quality of life, but curative strategies are greatly desired. In the past two decades, the therapeutic value of mesenchymal stromal cells (MSCs) has been evaluated because of their regenerative potential, which is mainly attributed to the secretion of paracrine factors. Many of these factors are enclosed in extracellular vesicles (EVs) that reproduce the main functions of parental cells. MSC-derived EVs have anti-inflammatory, anti-apoptotic as well as pro-regenerative activities. Research on EVs has gained considerable attention as they are a potential cell-free therapy with lower immunogenicity and easier management than whole cells. MSC-derived EVs can rescue the pathogenetic phenotypes of chondrocytes and exert a protective effect in animal models of rheumatic disease. To facilitate the therapeutic use of EVs, appropriate cell sources for the production of EVs with the desired biological effects in each disease should be identified. Production and isolation of EVs should be optimized, and pre-isolation and post-isolation modifications should be considered to maximize the disease-modifying potential of the EVs.
Topics: Animals; Humans; Middle Aged; Quality of Life; Extracellular Vesicles; Arthritis, Rheumatoid; Osteoarthritis; Mesenchymal Stem Cells
PubMed: 37666995
DOI: 10.1038/s41584-023-01010-7