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Arthritis Research & Therapy Nov 2023To determine the prevalence of sustained remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) after discontinuation of tumor necrosis factor...
Prevalence and predictors of sustained remission/low disease activity after discontinuation of induction or maintenance treatment with tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic and scoping review.
BACKGROUND
To determine the prevalence of sustained remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) after discontinuation of tumor necrosis factor inhibitors (TNFi), separately in induction treatment and maintenance treatment studies, and to identify predictors of successful discontinuation.
METHODS
We performed a systematic literature review of studies published from 2005 to May 2022 that reported outcomes after TNFi discontinuation among patients in remission/LDA. We computed prevalences of successful discontinuation by induction or maintenance treatment, remission criterion, and follow-up time. We performed a scoping review of predictors of successful discontinuation.
RESULTS
Twenty-two induction-withdrawal studies were identified. In pooled analyses, 58% (95% confidence interval (CI) 45, 70) had DAS28 < 3.2 (9 studies), 52% (95% CI 35, 69) had DAS28 < 2.6 (9 studies), and 40% (95% CI 18, 64) had SDAI ≤ 3.3 (4 studies) at 37-52 weeks after discontinuation. Among patients who continued TNFi, 62 to 85% maintained remission. Twenty-two studies of maintenance treatment discontinuation were also identified. At 37-52 weeks after TNFi discontinuation, 48% (95% CI 38, 59) had DAS28 < 3.2 (10 studies), and 47% (95% CI 33, 62) had DAS28 < 2.6 (6 studies). Heterogeneity among studies was high. Data on predictors in induction-withdrawal studies were limited. In both treatment scenarios, longer duration of RA was most consistently associated with less successful discontinuation.
CONCLUSIONS
Approximately one-half of patients with RA remain in remission/LDA for up to 1 year after TNFi discontinuation, with slightly higher proportions in induction-withdrawal settings than with maintenance treatment discontinuation.
Topics: Humans; Antirheumatic Agents; Tumor Necrosis Factor Inhibitors; Prevalence; Tumor Necrosis Factor-alpha; Remission Induction; Arthritis, Rheumatoid; Treatment Outcome
PubMed: 37986101
DOI: 10.1186/s13075-023-03199-0 -
Arthritis Research & Therapy Oct 2023Serum exosomes play important roles in intercellular communication and are promising biomarkers of several autoimmune diseases. However, the biological functions and...
BACKGROUND
Serum exosomes play important roles in intercellular communication and are promising biomarkers of several autoimmune diseases. However, the biological functions and potential clinical importance of long non-coding RNAs (lncRNAs) and mRNAs from serum exosomes in rheumatoid arthritis (RA) have not yet been studied.
METHODS
Serum exosomal lncRNAs and mRNAs were isolated from patients with RA and osteoarthritis (OA) and healthy controls. The differentially expressed lncRNAs (DE-lncRNAs) and mRNA profiles in the serum exosomes of patients with RA were analysed using high-throughput sequencing, and their functions were predicted using Gene Ontologyenrichment, Kyoto Encyclopedia of Genes and Genomes pathway, and gene set enrichment analysis. We constructed a DE-lncRNA-mRNA network and a protein-protein interaction network of differentially expressed mRNAs (DE-mRNAs) in RA using the Cytoscape software. The expression of several candidate a DE-lncRNAs and DE-mRNAs in the serum of patients with RA, patients with OA, and healthy controls was confirmed by qRT-PCR. We assessed the diagnostic ability of DE-lncRNAs and DE-mRNAs in patients with RA using receiver operating characteristic analysis. Furthermore, we analysed the characteristics of immune cell infiltration in RA by digital cytometry using the CIBERSORT algorithm and determined the correlation between immune cells and several DE-lncRNAs or DE-mRNAs in RA.
RESULTS
The profiles of serum exosomal lncRNAs and mRNAs in patients with RA were different from those in healthy controls and patients with OA. The functions of both DE-lncRNAs and DE-mRNAs in RA are associated with the immune response and cellular metabolic processes. The RT-PCR results show that NONHSAT193357.1, CCL5, and MPIG6B were downregulated in patients with RA. The combination of three DE-mRNAs, CCL5, MPIG6B, and PFKP, had an area under the curve of 0.845 for differentiating RA from OA. Digital cytometry using the CIBERSORT algorithm showed that the neutrophil counts were higher in patients with RA than those in healthy controls and patients with OA.
CONCLUSIONS
These findings help to elucidate the role of serum exosomal lncRNAs and mRNAs in the specific mechanisms underlying RA.
Topics: Humans; RNA, Long Noncoding; Exosomes; RNA, Messenger; Arthritis, Rheumatoid; Osteoarthritis; Gene Regulatory Networks; Gene Expression Profiling
PubMed: 37845777
DOI: 10.1186/s13075-023-03174-9 -
Italian Journal of Pediatrics Sep 2023Ataxia-telangiectasia (A-T) is a rare autosomal recessive DNA repair disorder, characterized by progressive cerebellar degeneration, telangiectasia, immunodeficiency,...
BACKGROUND
Ataxia-telangiectasia (A-T) is a rare autosomal recessive DNA repair disorder, characterized by progressive cerebellar degeneration, telangiectasia, immunodeficiency, recurrent sinopulmonary infections, radiation sensitivity, premature aging and predisposition to cancer. Although the association with autoimmune and chronic inflammatory conditions such as vitiligo, thrombocytopenia and arthritis has occasionally been reported, an onset with articular involvement at presentation is rare.
CASE PRESENTATION
We herein report the case of a 7-year-old Caucasian girl who was admitted to the Rheumatology Department with a history of febrile chough and polyarthritis which led initially to the suspicion of an autoinflammatory disease. She had overt polyarthritis with knees deformities and presented with severe pneumonia. A chest Computed Tomography (CT) scan showed bilateral bronchiectasis, parenchymal consolidation and interstitial lung disease; rheumatoid factor and type I interferon signature resulted negative, therefore excluding COatomer Protein subunit Alpha (COPA) syndrome. A diagnosis of sarcoidosis had been suspected based on histological evidence of granulomatous liver inflammation, but ruled out after detecting normal angiotensin converting enzyme and chitotriosidase blood levels. Based on her past medical history characterized by at least six episodes of pneumonia in the previous 4 years, immunological phenotyping was performed. This showed complete IgA and IgE deficiency with defective antigen-specific antibodies to Pneumococcal, Tetanus toxin and Hemophilus Influenzae B vaccines. Additionally, low numbers of B cells and recent thymic emigrants (RTE) were found (CD4Ra 1.4%), along with a low CD4+/CD8 + T cells ratio (< 1). Finally, based on gait disturbances (wobbly wide-based walking), serum alfa-fetoprotein was dosed, which resulted increased at 276 ng/ml (normal value < 7 ng/ml). A diagnosis of Ataxia-Telangiectasia was made, strengthened by the presence of bulbar telangiectasia, and then confirmed by Whole Exome Sequencing (WES).
CONCLUSIONS
Although rare, A-T should always be ruled out in case of pulmonary bronchiectasis and gait disturbances even in the absence of bulbar or skin telangiectasia. Autoimmune and granulomatous disorders must to be considered as differential diagnosis.
Topics: Female; Child; Humans; Ataxia Telangiectasia; Bronchiectasis; Arthritis; B-Lymphocytes; Lung Diseases
PubMed: 37667293
DOI: 10.1186/s13052-023-01509-5 -
Journal of the American Academy of... Feb 2024Psoriatic arthritis (PsA) is a chronic inflammatory disease that often goes unrecognized in patients with psoriasis. As a result, patients may develop significant... (Review)
Review
Psoriatic arthritis (PsA) is a chronic inflammatory disease that often goes unrecognized in patients with psoriasis. As a result, patients may develop significant structural damage before diagnosis and initiation of adequate treatment. Dermatologists are in an unique position to identify early signs and symptoms of PsA. Here, we briefly review the pathogenesis of PsA, differences in PsA presentation within real-world dermatology practice versus rheumatology clinical trials, and imaging modalities that can be used to assess structural damage. We then discuss several ongoing controversies related to prediction, assessment, and treatment of PsA-related structural damage. Debated questions include the following: (1) Does subclinical enthesitis predict progression from psoriasis to PsA?, (2) Does methotrexate inhibit progression of structural damage?, (3) Does structural damage correlate with clinical disease activity?, and (4) Can progression from psoriasis to PsA be prevented? Evidence presented herein suggests that dermatologists, together with rheumatologists, can play important roles in the early diagnosis and treatment of PsA, thereby potentially preventing irreversible structural damage.
Topics: Humans; Arthritis, Psoriatic; Dermatologists; Psoriasis; Rheumatology
PubMed: 37852305
DOI: 10.1016/j.jaad.2023.10.021 -
Theranostics 2024Lymphatic vessel networks are a main part of the vertebrate cardiovascular system, which participate in various physiological and pathological processes via regulation... (Review)
Review
Lymphatic vessel networks are a main part of the vertebrate cardiovascular system, which participate in various physiological and pathological processes via regulation of fluid transport and immunosurveillance. Targeting lymphatic vessels has become a potent strategy for treating various human diseases. The presence of varying degrees of inflammation in joints of rheumatoid arthritis (RA) and osteoarthritis (OA), characterized by heightened infiltration of inflammatory cells, increased levels of inflammatory factors, and activation of inflammatory signaling pathways, significantly contributes to the disruption of cartilage and bone homeostasis in arthritic conditions. Increasing evidence has demonstrated the pivotal role of lymphatic vessels in maintaining joint homeostasis, with their pathological alterations closely associated with the initiation and progression of inflammatory joint diseases. In this review, we provide a comprehensive overview of the evolving knowledge regarding the structural and functional aspects of lymphatic vessels in the pathogenesis of RA and OA. In addition, we summarized the potential regulatory mechanisms underlying the modulation of lymphatic function in maintaining joint homeostasis during inflammatory conditions, and further discuss the distinctions between RA and OA. Moreover, we describe therapeutic strategies for inflammatory arthritis based on lymphatic vessels, including the promotion of lymphangiogenesis, restoration of proper lymphatic vessel function through anti-inflammatory approaches, enhancement of lymphatic contractility and drainage, and alleviation of congestion within the lymphatic system through the elimination of inflammatory cells. At last, we envisage potential research perspectives and strategies to target lymphatic vessels in treating these inflammatory joint diseases.
Topics: Humans; Arthritis, Rheumatoid; Osteoarthritis; Lymphatic Vessels; Inflammation; Lymphangiogenesis
PubMed: 38164153
DOI: 10.7150/thno.90940 -
Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation.The Journal of Experimental Medicine Aug 2023The first immune-activating changes within joint resident cells that lead to pathogenic leukocyte recruitment during articular inflammation remain largely unknown. In...
The first immune-activating changes within joint resident cells that lead to pathogenic leukocyte recruitment during articular inflammation remain largely unknown. In this study, we employ state-of-the-art confocal microscopy and image analysis in a systemic, whole-organ, and quantitative way to present evidence that synovial inflammation begins with the activation of lining macrophages. We show that lining, but not sublining macrophages phagocytose immune complexes containing the model antigen. Using the antigen-induced arthritis (AIA) model, we demonstrate that on recognition of antigen-antibody complexes, lining macrophages undergo significant activation, which is dependent on interferon regulatory factor 5 (IRF5), and produce chemokines, most notably CXCL1. Consequently, at the onset of inflammation, neutrophils are preferentially recruited in the vicinity of antigen-laden macrophages in the synovial lining niche. As inflammation progresses, neutrophils disperse across the whole synovium and form swarms in synovial sublining during resolution. Our study alters the paradigm of lining macrophages as immunosuppressive cells to important instigators of synovial inflammation.
Topics: Humans; Neutrophil Infiltration; Arthritis; Macrophages; Synovial Membrane; Inflammation; Antigens
PubMed: 37115585
DOI: 10.1084/jem.20220595 -
Arthritis Research & Therapy Oct 2023In European axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) clinical registries, we aimed to investigate commonalities and differences in (1) set-up,...
BACKGROUND
In European axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) clinical registries, we aimed to investigate commonalities and differences in (1) set-up, clinical data collection; (2) data availability and completeness; and (3) wording, recall period, and scale used for selected patient-reported outcome measures (PROMs).
METHODS
Data was obtained as part of the EuroSpA Research Collaboration Network and consisted of (1) an online survey and follow-up interview, (2) upload of real-world data, and (3) selected PROMs included in the online survey.
RESULTS
Fifteen registries participated, contributing 33,948 patients (axSpA: 21,330 (63%), PsA: 12,618 (37%)). The reported coverage of eligible patients ranged from 0.5 to 100%. Information on age, sex, biological/targeted synthetic disease-modifying anti-rheumatic drug treatment, disease duration, and C-reactive protein was available in all registries with data completeness between 85% and 100%. All PROMs (Bath Ankylosing Spondylitis Disease Activity and Functional Indices, Health Assessment Questionnaire, and patient global, pain and fatigue assessments) were more complete after 2015 (68-86%) compared to prior (50-79%). Patient global, pain and fatigue assessments showed heterogeneity between registries in terms of wording, recall periods, and scale.
CONCLUSION
Important heterogeneity in registry design and data collection across fifteen European axSpA and PsA registries was observed. Several core measures were widely available, and an increase in data completeness of PROMs in recent years was identified. This study might serve as a basis for examining how differences in data collection across registries may impact the results of collaborative research in the future.
Topics: Humans; Arthritis, Psoriatic; Spondylarthritis; Spondylitis, Ankylosing; Registries; Pain
PubMed: 37858143
DOI: 10.1186/s13075-023-03184-7 -
Frontiers in Immunology 2023Ankylosing spondylitis (AS) is a rheumatic and autoimmune disease associated with a chronic inflammatory response, mainly characterized by pain, stiffness, or limited...
BACKGROUND
Ankylosing spondylitis (AS) is a rheumatic and autoimmune disease associated with a chronic inflammatory response, mainly characterized by pain, stiffness, or limited mobility of the spine and sacroiliac joints. Severe symptoms can lead to joint deformity, destruction, and even lifelong disability, causing a serious burden on families and society as a whole. A large number of clinical studies have been published on AS over the past 20 years. This study aimed to summarize the current research status and global trends relating to AS clinical trials through a bibliometric analysis.
METHODS
The Web of Science Core Collection database was searched for publications related to AS clinical trials published between January 2003 and June 2023. Bibliometric analysis and web visualization were performed using CiteSpace, VOSviewer, and a bibliometric online analysis platform (https://bibliometric.com), which included the number of publications, citations, countries, institutions, journals, authors, references, and keywords.
RESULTS
1,212 articles published in 201 journals from 65 countries were included in this study. The number of publications related to AS clinical trials is increasing annually. The United States and the Free University of Berlin, the countries and institutions, respectively, that have published the most articles on AS, have made outstanding contributions to this field. The author with the most published papers and co-citations over the period covered by the study was Desiree Van Der Heijde. The journal with the most published and cited articles was Annals of the Rheumatic Diseases. The keywords: "double-blind," "rheumatoid arthritis," "efficacy," "placebo-controlled trial," "infliximab," "etanercept," "psoriatic arthritis" and "therapy" represent the current research hotspots regarding AS.
DISCUSSION
This is the first study to perform a bibliometric analysis and visualization of AS clinical trial publications, providing a reliable research focus and direction for clinicians. Future studies in the field of AS clinical trials should focus on placebo-controlled trials of targeted therapeutic drugs.
Topics: Humans; Arthritis, Rheumatoid; Autoimmune Diseases; Bibliometrics; Etanercept; Spondylitis, Ankylosing
PubMed: 38288126
DOI: 10.3389/fimmu.2023.1328439 -
Ageing Research Reviews Mar 2024Arthritis has become the most common joint disease globally. Current attention has shifted towards preventing the disease and exploring pharmaceutical and surgical... (Review)
Review
Arthritis has become the most common joint disease globally. Current attention has shifted towards preventing the disease and exploring pharmaceutical and surgical treatments for early-stage arthritis. M2 macrophages are known for their anti-inflammatory properties and their ability to support cartilage repair, offering relief from arthritis. Whereas, it remains a great challenge to promote the beneficial secretion of M2 macrophages to prevent the progression of arthritis. Therefore, it is warranted to investigate new strategies that could use the functions of M2 macrophages and enhance its therapeutic effects. This review aims to explore the macrophage cell membrane-coated biomimetic nanovesicles for targeted treatment of arthritis such as osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA). Cell membrane-camouflaged biomimetic nanovesicle has attracted increasing attention, which successfully combine the advantages and properties of both cell membrane and delivered drug. We discuss the roles of macrophages in the pathophysiology and therapeutic targets of arthritis. Then, the common preparation strategies of macrophage membrane-coated nanovesicles are concluded. Moreover, we investigate the applications of macrophage cell membrane-camouflaged nanovesicles for arthritis, such as OA, RA, and GA. Taken together, macrophage cell membrane-camouflaged nanovesicles hold the tremendous prospect for biomedical applications in the targeted treatment of arthritis.
Topics: Humans; Biomimetics; Arthritis, Rheumatoid; Macrophages; Osteoarthritis
PubMed: 38387516
DOI: 10.1016/j.arr.2024.102241 -
Communications Biology Oct 2023Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Ethanol consumption has been reported to reduce morbidity in RA patients, but the mechanism behind it...
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Ethanol consumption has been reported to reduce morbidity in RA patients, but the mechanism behind it remains unclear. Our results showed that Muribaculaceae was predominant in the gut microbiota of mice after ethanol treatment, and the levels of microbiota metabolite acetate were increased. Acetate reduced arthritis severity in collagen-induced arthritis (CIA) mice, which was associated with a decrease in the articular neutrophils and the myeloperoxidase-deoxyribonucleic acid complex in serum. Meanwhile, in vitro experiments confirmed that acetate affected neutrophil activity by acting on G-protein-coupled receptor 43, which reduced endoplasmic reticulum stress in neutrophils and inhibited neutrophil extracellular traps formation. Furthermore, exogenous acetate reversed CIA mice with exacerbated gut microbial disruption, further confirming that the effect of gut microbial metabolite acetate on neutrophils in vivo is crucial for the immune regulation. Our findings illuminate the metabolic and cellular mechanisms of the gut-joint axis in the regulation of autoimmune arthritis, and may offer alternative avenues to replicate or induce the joint-protective benefits of ethanol without associated detrimental effects.
Topics: Humans; Mice; Animals; Extracellular Traps; Arthritis, Rheumatoid; Neutrophils; Arthritis, Experimental; Acetates
PubMed: 37884797
DOI: 10.1038/s42003-023-05473-y