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Autoimmunity Reviews Nov 2023Autoimmune diseases have specific pathophysiologic mechanisms leading to an increased risk of arterial and venous thrombosis. The risk of venous thromboembolism (VTE)... (Review)
Review
Autoimmune diseases have specific pathophysiologic mechanisms leading to an increased risk of arterial and venous thrombosis. The risk of venous thromboembolism (VTE) varies according to the type and stage of the disease, and to concomitant treatments. In this review, we revise the most common autoimmune disease such as antiphospholipid syndrome, inflammatory myositis, polymyositis and dermatomyositis, rheumatoid arthritis, sarcoidosis, Sjogren syndrome, autoimmune haemolytic anaemia, systemic lupus erythematosus, systemic sclerosis, vasculitis and inflammatory bowel disease. We also provide an overview of pathophysiology responsible for the risk of VTE in each autoimmune disorder, and report current indications to anticoagulant treatment for primary and secondary prevention of VTE.
Topics: Humans; Venous Thromboembolism; Autoimmune Diseases; Arthritis, Rheumatoid; Antiphospholipid Syndrome; Lupus Erythematosus, Systemic
PubMed: 37714419
DOI: 10.1016/j.autrev.2023.103447 -
International Immunopharmacology Aug 2023Chemokine receptor 7 (CCR7) is a G protein-coupled receptor containing 7 transmembrane domains that is expressed on various cells, such as naive T/B cells, central... (Review)
Review
Chemokine receptor 7 (CCR7) is a G protein-coupled receptor containing 7 transmembrane domains that is expressed on various cells, such as naive T/B cells, central memory T cells, regulatory T cells, immature/mature dendritic cells (DCs), natural killer cells, and a minority of tumor cells. Chemokine ligand 21 (CCL21) is the known high-affinity ligand that binds to CCR7 and drives cell migration in tissues. CCL21 is mainly produced by stromal cells and lymphatic endothelial cells, and its expression is significantly increased under inflammatory conditions. Genome-wide association studies (GWAS) have shown a strong association between CCL21/CCR7 axis and disease severity in patients with rheumatoid arthritis, sjogren's syndrome, systemic lupus erythematosus, polymyositis, ankylosing spondylitis, and asthma. Disrupting CCL21/CCR7 interaction with antibodies or inhibitors prevents the migration of CCR7-expressing immune and non-immune cells at the site of inflammation and reduces disease severity. This review emphasizes the importance of the CCL21 /CCR7 axis in autoimmune diseases and evaluates its potential as a novel therapeutic target for these conditions.
Topics: Humans; Receptors, CCR7; Chemokine CCL21; Ligands; Endothelial Cells; Genome-Wide Association Study; Autoimmune Diseases; Chemokines; Cell Movement
PubMed: 37331295
DOI: 10.1016/j.intimp.2023.110431 -
EMBO Molecular Medicine Oct 2023Idiopathic inflammatory myopathies (IIM), also referred to as "myositis," are a group of heterogeneous autoimmune disorders characterised by muscle weakness, atrophy and...
Idiopathic inflammatory myopathies (IIM), also referred to as "myositis," are a group of heterogeneous autoimmune disorders characterised by muscle weakness, atrophy and progressive reduced mobility (Lundberg et al, 2021). IIM represent a significant health burden in adult populations, affecting individuals at a mean age of 50 with an estimated prevalence of 2.9-34 per 100,000 (Dobloug et al, 2015; Svensson et al, 2017). IIM encompass several subtypes including dermatomyositis, immune-mediated necrotising myopathy, inclusion-body myositis, antisynthetase syndrome and polymyositis, which are characterised by specific clinical features, histopathological findings and autoantibody status (Pinal-Fernandez et al, 2020).
Topics: Adult; Humans; Middle Aged; Dermatomyositis; T-Lymphocytes; Myositis; Myositis, Inclusion Body; Autoimmune Diseases; Sequence Analysis, RNA
PubMed: 37768011
DOI: 10.15252/emmm.202318190 -
Circulation Research Jun 2024Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus... (Review)
Review
Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even in cases of myocarditis caused by viral infections, dysregulated immune responses contribute to pathogenesis. However, whether triggered by existing autoimmune conditions or viral infections, the precise antigens and immunologic pathways driving myocarditis remain incompletely understood. The emergence of myocarditis associated with immune checkpoint inhibitor therapy, commonly used for treating cancer, has afforded an opportunity to understand autoimmune mechanisms in myocarditis, with autoreactive T cells specific for cardiac myosin playing a pivotal role. Despite their self-antigen recognition, cardiac myosin-specific T cells can be present in healthy individuals due to bypassing the thymic selection stage. In recent studies, novel modalities in suppressing the activity of pathogenic T cells including cardiac myosin-specific T cells have proven effective in treating autoimmune myocarditis. This review offers an overview of the current understanding of heart antigens, autoantibodies, and immune cells as the autoimmune mechanisms underlying various forms of myocarditis, along with the latest updates on clinical management and prospects for future research.
Topics: Myocarditis; Humans; Autoimmune Diseases; Animals; Autoantibodies; Autoimmunity; T-Lymphocytes; Autoantigens; Cardiac Myosins
PubMed: 38843292
DOI: 10.1161/CIRCRESAHA.124.323816 -
Cureus Aug 2023Inflammatory myopathies are a group of diseases whose common pathway is immune-mediated muscle damage, one of which is polymyositis. The definition of polymyositis is...
Inflammatory myopathies are a group of diseases whose common pathway is immune-mediated muscle damage, one of which is polymyositis. The definition of polymyositis is controversial, with proponents advocating a definition based on immunohistochemical and histopathological findings in muscle biopsies, while other proponents advocate a definition based on clinical manifestations and histopathological findings. Polymyositis is a quite rare disease that is clinically characterized by progressive proximal muscle weakness with a symmetric distribution. Within the diagnostic approach, laboratory studies show elevation of sarcoplasmic enzymes; nerve conduction tests are performed, which may aid in distinguishing myopathic causes of weakness from neuropathic disorders; and muscle biopsy is considered the gold standard to diagnose inflammatory myopathy and to distinguish the subclasses. We report the case of a 61-year-old male patient who presented generalized symmetrical weakness, predominantly in the upper extremities, and dysphagia, whose laboratory studies, autoantibodies, and muscle biopsy were confirmatory of this entity.
PubMed: 37700938
DOI: 10.7759/cureus.43337 -
Briefings in Bioinformatics Nov 2023Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of muscle disorders including adult and juvenile dermatomyositis, polymyositis, immune-mediated... (Review)
Review
Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of muscle disorders including adult and juvenile dermatomyositis, polymyositis, immune-mediated necrotising myopathy and sporadic inclusion body myositis, all of which present with variable symptoms and disease progression. The identification of effective biomarkers for IIMs has been challenging due to the heterogeneity between IIMs and within IIM subgroups, but recent advances in machine learning (ML) techniques have shown promises in identifying novel biomarkers. This paper reviews recent studies on potential biomarkers for IIM and evaluates their clinical utility. We also explore how data analytic tools and ML algorithms have been used to identify biomarkers, highlighting their potential to advance our understanding and diagnosis of IIM and improve patient outcomes. Overall, ML techniques have great potential to revolutionize biomarker discovery in IIMs and lead to more effective diagnosis and treatment.
Topics: Adult; Humans; Myositis; Dermatomyositis; Autoimmune Diseases; Biomarkers; Disease Progression
PubMed: 38243695
DOI: 10.1093/bib/bbad514 -
Annals of the Rheumatic Diseases Jun 2024With improved understanding of disease pathogenesis and availability of outcome measures, there has been a remarkable increase in the number of therapeutic clinical...
With improved understanding of disease pathogenesis and availability of outcome measures, there has been a remarkable increase in the number of therapeutic clinical trials in idiopathic inflammatory myopathies (myositis) over the last three years reaching as many as five trials per site. These trials share similar design and inclusion/exclusion criteria resulting in a competitive clinical trial landscape in myositis. While these are exciting times for the myositis field, we have a number of concerns about the design and conduct of the myositis trials. These include competitive landscape, lengthy placebo arms, underrepresentation of minority groups among participants, use of patient reported outcome measures with limited/no data on validity in myositis, antiquated disease classification criteria, and unclear performance of the ACR/EULAR Myositis Response Criteria in skin-predominant patients despite inclusion of these patients in trials. In this viewpoint, we further discuss these concerns and offer potential solutions such as including patient perspectives in the trial design and adoption of innovative frameworks.
Topics: Humans; Clinical Trials as Topic; Myositis; Patient Reported Outcome Measures; Research Design
PubMed: 38216318
DOI: 10.1136/ard-2023-224652 -
Scientific Reports Oct 2023Dermatomyositis and polymyositis are rare, idiopathic inflammatory myopathies. Interstitial lung disease is one of the most common and potentially severe extra-muscular...
Dermatomyositis and polymyositis are rare, idiopathic inflammatory myopathies. Interstitial lung disease is one of the most common and potentially severe extra-muscular manifestations of dermatomyositis and polymyositis and is strongly linked to poor prognosis and early mortality. We aimed to characterise the demographic and clinical characteristics, incidence, and treatment of interstitial lung disease in patients with dermatomyositis or polymyositis. We conducted a retrospective cohort study using the Japan Medical Data Center healthcare claims database. Patients in the database with dermatomyositis (International Classification of Disease version 10 M33.0, M33.1, M33.9) or polymyositis (M33.2) from 01-Jan-2011 until 31-Dec-2019 were identified and followed-up for interstitial lung disease (J84.x) until death, dis-enrolment, or study end (31 December 2020). Cumulative risk curves compared interstitial lung disease risk in dermatomyositis versus polymyositis. Risk factors were evaluated by Cox proportional hazard models. There were 886 patients with dermatomyositis and 745 patients with polymyositis included in the cohort analysis. Mean (standard deviation) age at dermatomyositis/polymyositis diagnosis was 46.0 (16.0)/49.7 (13.3) years and 300 (34%)/104 (14%) developed interstitial lung disease during follow-up. The incidence rate of interstitial lung disease per 100 person-years was 18.42 (95% CI 16.42-20.59) for dermatomyositis and 5.39 (95% CI 4.43-6.50) for polymyositis. In the analysis adjusted for sex, age, and comorbidity score, the risk of interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis (hazard ratio 2.72, 95% CI 2.18-3.41). The rate diverged markedly between the groups in the first year after diagnosis. Risk factors for interstitial lung disease were older age in dermatomyositis, female sex and rheumatoid arthritis in polymyositis. Glucocorticoids with/without tacrolimus were the most common newly prescribed drugs after the interstitial lung disease diagnosis. In conclusion, the risk of developing interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis, and risk factors were different in the 2 patient groups.
Topics: Humans; Female; Dermatomyositis; Retrospective Studies; Japan; Polymyositis; Lung Diseases, Interstitial; Cohort Studies; Prognosis
PubMed: 37821555
DOI: 10.1038/s41598-023-44092-9 -
Journal of Clinical Medicine Sep 2023Dysferlinopathy is a disease caused by a dysferlin deficiency due to mutations in the gene. Dysferlin is a membrane protein in the sarcolemma and is involved in... (Review)
Review
Dysferlinopathy is a disease caused by a dysferlin deficiency due to mutations in the gene. Dysferlin is a membrane protein in the sarcolemma and is involved in different functions, such as membrane repair and vesicle fusion, T-tubule development and maintenance, Ca signalling, and the regulation of various molecules. Miyoshi Myopathy type 1 (MMD1) and Limb-Girdle Muscular Dystrophy 2B/R2 (LGMD2B/LGMDR2) are two possible clinical presentations, yet the same mutations can cause both presentations in the same family. They are therefore grouped under the name dysferlinopathy. Onset is typically during the teenage years or young adulthood and is characterized by a loss of Achilles tendon reflexes and difficulty in standing on tiptoes or climbing stairs, followed by a slow progressive loss of strength in limb muscles. The MRI pattern of patient muscles and their biopsies show various fibre sizes, necrotic and regenerative fibres, and fat and connective tissue accumulation. Recent tools were developed for diagnosis and research, especially to evaluate the evolution of the patient condition and to prevent misdiagnosis caused by similarities with polymyositis and Charcot-Marie-Tooth disease. The specific characteristic of dysferlinopathy is dysferlin deficiency. Recently, mouse models with patient mutations were developed to study genetic approaches to treat dysferlinopathy. The research fields for dysferlinopathy therapy include symptomatic treatments, as well as antisense-mediated exon skipping, myoblast transplantation, and gene editing.
PubMed: 37762951
DOI: 10.3390/jcm12186011 -
Frontiers in Immunology 2023We aimed to identify B-cell-mediated immunomechanisms in inclusion body myositis (IBM) and polymyositis (PM) as part of the complex pathophysiology.
INTRODUCTION
We aimed to identify B-cell-mediated immunomechanisms in inclusion body myositis (IBM) and polymyositis (PM) as part of the complex pathophysiology.
MATERIALS AND METHODS
Human primary myotube cultures were derived from orthopedic surgery. Diagnostic biopsy specimens from patients with IBM (n=9) and PM (n=9) were analyzed for markers of B cell activation (BAFF and APRIL) and for chemokines that control the recruitment of B cells (CXCL-12 and CXCL-13). Results were compared to biopsy specimens without myopathic changes (n=9) and hereditary muscular dystrophy (n=9).
RESULTS
The mRNA expression of BAFF, APRIL, and CXCL-13 was significantly higher in IBM and PM compared to controls. Patients with IBM displayed the highest number of double positive muscle fibers for BAFF and CXCL-12 (48%) compared to PM (25%), muscular dystrophy (3%), and non-myopathic controls (0%). , exposure of human myotubes to pro-inflammatory cytokines led to a significant upregulation of BAFF and CXCL-12, but APRIL and CXCL-13 remained unchanged.
CONCLUSION
The results substantiate the hypothesis of an involvement of B cell-associated mechanisms in the pathophysiology of IBM and PM. Muscle fibers themselves seem to contribute to the recruitment of B cells and sustain inflammation.
Topics: Humans; Myositis; Polymyositis; Myositis, Inclusion Body; Inflammation; Muscle Fibers, Skeletal
PubMed: 37731487
DOI: 10.3389/fimmu.2023.1177721