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International Journal of Molecular... Sep 2022CD8 T cells are cytotoxic lymphocytes that destroy pathogen infected and malignant cells through release of cytolytic molecules and proinflammatory cytokines. Although... (Review)
Review
CD8 T cells are cytotoxic lymphocytes that destroy pathogen infected and malignant cells through release of cytolytic molecules and proinflammatory cytokines. Although the role of CD8 T cells in connective tissue diseases (CTDs) has not been explored as thoroughly as that of other immune cells, research focusing on this key component of the immune system has recently gained momentum. Aberrations in cytotoxic cell function may have implications in triggering autoimmunity and may promote tissue damage leading to exacerbation of disease. In this comprehensive review of current literature, we examine the role of CD8 T cells in systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, polymyositis, and dermatomyositis with specific focus on comparing what is known about CD8 T cell peripheral blood phenotypes, CD8 T cell function, and CD8 T cell organ-specific profiles in adult and juvenile forms of these disorders. Although, the precise role of CD8 T cells in the initiation of autoimmunity and disease progression remains to be elucidated, increasing evidence indicates that CD8 T cells are emerging as an attractive target for therapy in CTDs.
Topics: CD8-Positive T-Lymphocytes; Connective Tissue Diseases; Cytokines; Humans; Lupus Erythematosus, Systemic; Phenotype; Polymyositis; Scleroderma, Systemic; Sjogren's Syndrome
PubMed: 36232733
DOI: 10.3390/ijms231911431 -
Arthritis & Rheumatology (Hoboken, N.J.) Jun 2023The idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases thought to be initiated by immune activation in genetically predisposed individuals. We imputed...
OBJECTIVE
The idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases thought to be initiated by immune activation in genetically predisposed individuals. We imputed variants from the ImmunoChip array using a large reference panel to fine-map associations and identify novel associations in IIM.
METHODS
We analyzed 2,565 Caucasian IIM patient samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically matched control samples. We imputed 1,648,116 variants from the ImmunoChip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM and clinical and serologic subgroups.
RESULTS
The HLA locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, SDK2 and LINC00924 (both novel) and STAT4 in the whole IIM cohort, with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and for CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells.
CONCLUSION
We found novel and strong associations in IIM and PM and localized signals to single genes and immune cell types.
Topics: Humans; Myositis; Polymyositis; Autoimmune Diseases; Genetic Predisposition to Disease; Haplotypes
PubMed: 36580032
DOI: 10.1002/art.42434 -
Aging May 2022Polymyositis (PM) and dermatomyositis (DM) are heterogeneous disorders. However, the etiology of PM/DM development has not been thoroughly clarified.
OBJECTIVE
Polymyositis (PM) and dermatomyositis (DM) are heterogeneous disorders. However, the etiology of PM/DM development has not been thoroughly clarified.
METHODS
Gene expression data of PM/DM were obtained from Gene Expression Omnibus. We used robust rank aggregation (RRA) to identify differentially expressed genes (DEGs). Gene Ontology functional enrichment and pathway analyses were used to investigate potential functions of the DEGs. Weighted gene co-expression network analysis (WGCNA) was used to establish a gene co-expression network. CIBERSORT was utilized to analyze the pattern of immune cell infiltration in PM/DM. Protein-protein interaction (PPI) network, Venn, and association analyses between core genes and muscle injury were performed to identify hub genes. Receiver operating characteristic analyses were executed to investigate the value of hub genes in the diagnosis of PM/DM, and the results were verified using the microarray dataset GSE48280.
RESULTS
Five datasets were included. The RRA integrated analysis identified 82 significant DEGs. Functional enrichment analysis revealed that immune function and the interferon signaling pathway were enriched in PM/DM. WGCNA outcomes identified MEblue and MEturquoise as key target modules in PM/DM. Immune cell infiltration analysis revealed greater macrophage infiltration and lower regulatory T-cell infiltration in PM/DM patients than in healthy controls. PPI network, Venn, and association analyses of muscle injury identified five putative hub genes: , , , , and .
CONCLUSIONS
Our bioinformatics analysis identified new genetic biomarkers of the pathogenesis of PM/DM. We demonstrated that immune cell infiltration plays a pivotal part in the occurrence of PM/DM.
Topics: Biomarkers; Computational Biology; Dermatomyositis; Gene Expression Profiling; Gene Regulatory Networks; Genetic Markers; Humans; Polymyositis
PubMed: 35609018
DOI: 10.18632/aging.204098 -
Biomedical Papers of the Medical... Mar 2016Rheumatic diseases are commonly considered chronic conditions. However, acute manifestations can be very severe and represent a diagnostic problem. Examples are systemic... (Review)
Review
BACKGROUND AND AIM
Rheumatic diseases are commonly considered chronic conditions. However, acute manifestations can be very severe and represent a diagnostic problem. Examples are systemic lupus erythematosus with acute flare, glomerulonephritis, CNS disorders and catastrophic antiphospholipid syndrome, scleroderma with interstitial lung disease, pulmonary hypertension and renal crisis and polyangiitis with alveolar haemorhage and acute respiratory failure. This aim of this paper is to overview emergency situations which can be encountered in the care of patients with autoimmune systemic diseases and vasculitides.
METHODS
A Pubmed search for both original and review articles, recent textbooks and current guidelines related to rheumatic diseases with possible acute situations were included in this review article. Relevant image documentation was obtained at the site over the past several years of observation.
CONCLUSIONS
This paper provides an overview of facts and emergency situations which can be encountered in the care of patients with autoimmune systemic diseases and vasculitides. It is directed at clinicians working in intensive care. It provides a differential diagnostic overview and information which is rare and commonly underestimated.
Topics: Acute Disease; Autoimmune Diseases; Cardiovascular Diseases; Central Nervous System Diseases; Dermatomyositis; Emergencies; Female; Humans; Kidney Diseases; Lung Diseases; Pregnancy; Prognosis; Rheumatic Diseases; Seizures
PubMed: 26868300
DOI: 10.5507/bp.2016.002 -
Medicine Apr 2023We aimed to determine the association between disease activity during pregnancy and pregnancy outcomes of women with polymyositis and dermatomyositis (PM/DM). Patients...
We aimed to determine the association between disease activity during pregnancy and pregnancy outcomes of women with polymyositis and dermatomyositis (PM/DM). Patients with PM/DM who were managed from pregnancy to delivery at Kagawa University Hospital from March 2006 to May 2021 were enrolled. Clinical data were retrospectively analyzed to evaluate the association between disease activity during pregnancy and pregnancy outcomes. Eight pregnancies in 5 women with PM/DM were analyzed. The mean age at conception was 28.3 ± 3.8 years, and mean disease duration was 6.3 ± 3.2 years. Four patients required an increased glucocorticoid dosage because of worsening disease activity (sustained elevation of creatine phosphokinase [CPK] concentration). Two patients who continuously received immunosuppressive drugs from conception to delivery showed no increase in disease activity and did not need increased glucocorticoid dosages. The pregnancy outcomes were 1 spontaneous abortion and 7 live births. The mean gestation length was 35.3 ± 5.2 weeks, and mean birthweight was 2297.7 ± 1041.4 g. Five adverse pregnancy outcomes (APOs) occurred (2 preterm births and 4 low birthweights); most of these cases had sustained elevation of CPK concentration and increased glucocorticoid dosages. No APOs occurred in the 2 patients who received continuous immunosuppressive medication. Continued use of pregnancy-compatible medications and control of disease activity with lower glucocorticoid dosages in pregnancies with PM/DM may be important to achieve good pregnancy outcomes.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Dermatomyositis; Polymyositis; Glucocorticoids; Retrospective Studies; Pregnancy Outcome
PubMed: 37026900
DOI: 10.1097/MD.0000000000033462 -
Frontiers in Immunology 2020Growing evidence from studies elsewhere have illustrated that microRNAs (miRNAs) play important roles in polymyositis and dermatomyositis (PM/DM). However, little has...
Growing evidence from studies elsewhere have illustrated that microRNAs (miRNAs) play important roles in polymyositis and dermatomyositis (PM/DM). However, little has been reported on their relationship with regenerating islet-derived protein 3-alpha (REG3A) as well as their associative roles in macrophage migration. Therefore, this study sought to establish the association between miR-146a and REG3A as well as investigate their functional roles in macrophage migration and PM/DM pathogenesis. Peripheral blood mononuclear cells (PBMCs) were isolated from PM/DM patients and healthy controls through density centrifugation. Macrophages were obtained from monocytes purified from PBMCs via differentiation before their transfection with miRNA or plasmids to investigate cell migration with transwell assay. An experimental autoimmune myositis murine model was used to investigate PM/DM. Real-time PCR and Western blot analysis were conducted to determine the expression levels of miR-146a, interferon gamma (IFN-γ), interleukin (IL)-17A, and REG3A. The messenger RNA (mRNA) expression level of miR-146a markedly decreased, while the mRNA level of REG3A, IFN-γ, and IL-17A expression increased substantially in PBMCs from PM/DM patients compared with the healthy controls. The levels of IFN-γ and IL-17A in serum from PM/DM patients was much higher than the healthy controls. Immunohistochemistry analysis showed that REG3A expression increased in muscle tissues from patients. Consistent with clinical data, the mRNA expression level of miR-146a also decreased, whereas the mRNA and protein level of REG3A, IFN-γ, and IL-17A significantly increased in the muscle tissues of experimental autoimmune myositis mice. Moreover, miR-146a inhibited monocyte-derived macrophage migration, and REG3A promoted macrophage migration. In addition, IL-17A induced REG3A expression, while miR146a inhibited expression of REG3A in monocyte-derived macrophages from the PBMCs of the healthy donors. Notably, inhibition of macrophage migration by miR-146a was via the reduction in REG3A expression. Reduced miR-146a expression in PM/DM leads to increased REG3A expression that increases inflammatory macrophage migration, which may be a possible underlying mechanism of DM/PM pathogenesis.
Topics: Adult; Animals; Case-Control Studies; Cell Movement; Dermatomyositis; Female; Humans; Macrophages; Male; Mice; Mice, Inbred BALB C; MicroRNAs; Middle Aged; Nervous System Autoimmune Disease, Experimental; Pancreatitis-Associated Proteins; Plasmids; Polymyositis; RNA, Messenger; Transfection; Young Adult
PubMed: 32153557
DOI: 10.3389/fimmu.2020.00037 -
Annals of Palliative Medicine Jul 2020Polymyositis (PM) and dermatomyositis (DM) are autoimmune diseases characterized by inflammation of skeletal muscle, primarily manifesting as chronic muscle weakness.... (Review)
Review
Polymyositis (PM) and dermatomyositis (DM) are autoimmune diseases characterized by inflammation of skeletal muscle, primarily manifesting as chronic muscle weakness. Extramuscular organs can also be affected. Cardiac involvement is one of the visceral organ damages whose prevalence is underestimated and is a marker of poor prognosis leading to irreversible dysfunction or even death. Although early and accurate recognition of cardiac involvement remains a key barrier to improving survival in PM/ DM patients, considerable progress has been made, and an overview will be provided in this review. The new concept of multimodality imaging, which involves an integrated approach of echocardiography (Echo), cardiac magnetic resonance and sometimes positron emission tomography (PET), can facilitate diagnosis. The development of ultrasound technology, including strain analysis, stress Echo and contrast-enhanced Echo, helps disclose early cardiac dysfunction more sensitively than conventional Echo. Cardiac magnetic resonance unveils silent, acute or chronic myocarditis in PM/DM and is used to monitor treatment efficacy due to its excellent tissue characterization. PET can be useful thanks to the appearance of new tracers that can eliminate the effects of glucose uptake by normal cardiomyocytes. The sensitivity of endomyocardial biopsy may be increased by targeted sampling with the guidance of cardiac imaging. Troponin I is specific to cardiac injury, and investigations into antibodies against cardiac tissue are being carried out. Disease-specific mechanisms and therapies are also discussed to give more insights into cardiac involvement in PM and DM.
Topics: Dermatomyositis; Heart; Humans; Inflammation; Muscle, Skeletal; Polymyositis
PubMed: 32648461
DOI: 10.21037/apm-19-650 -
Anais Brasileiros de Dermatologia 2018There are scarce studies in the literature about hyaluronic acid in systemic autoimmune myopathies.
BACKGROUND
There are scarce studies in the literature about hyaluronic acid in systemic autoimmune myopathies.
OBJECTIVES
To analyze the serum level of hyaluronic acid in patients with dermatomyositis and polymyositis.
METHODS
Cross-sectional study, single-center, that evaluated hyaluronic acid in 18 dermatomyositis and 15 polymyositis (Bohan and Peter criteria), newly diagnosed, with clinical and laboratory activity, with no previous drug treatment. The patients were also age-, gender- and ethnicity-matched to 36 healthy individuals. The hyaluronic acid was analyzed by ELISA/EIA kit anti-hyaluronic acid.
RESULTS
There was a higher serum level of hyaluronic acid in patients with autoimmune myopathies, in relation to control group (P<0.05). Moreover, the serum level of this glycosaminoglycan was higher in dermatomyositis, when compared to polymyositis. Both groups were comparable with regard to demographic, clinical and laboratory data, except for the presence of skin lesions in the first group.
STUDY LIMITATIONS
The presence of hyaluronic acid in cutaneous lesions, particularly of patients with dermatomyositis, was not analyzed neither quantified. In addition, due to disease rarity and the establishment of strict inclusion and exclusion criteria, there was a small sample in the present study.
CONCLUSIONS
As an example of others systemic autoimmune diseases, it is possible that the hyaluronic acid is involved in the pathogenesis of autoimmune myopathies, and particularly when associated with cutaneous lesions.
Topics: Adult; Creatine Kinase; Cross-Sectional Studies; Dermatomyositis; Female; Fructose-Bisphosphate Aldolase; Humans; Hyaluronic Acid; Male; Middle Aged; Polymyositis
PubMed: 29641701
DOI: 10.1590/abd1806-4841.20186727 -
Revista Brasileira de Reumatologia 2016Cardiac involvement is frequent in inflammatory myopathies. Electrocardiogram (ECG) may show evidence of this involvement and its changes should be well-known and...
INTRODUCTION
Cardiac involvement is frequent in inflammatory myopathies. Electrocardiogram (ECG) may show evidence of this involvement and its changes should be well-known and described.
OBJECTIVES
Due to the lack of studies in the literature, we conducted an analysis of the ECG findings in patients with dermatomyositis (DM) and polymyositis (PM), comparing them with a control group.
METHODS
This cross-sectional study compared the ECG of 86 individuals with no rheumatic disorders (controls) with 112 patients (78 DM and 34 PM), during 2010-2013. The ECG findings between DM and PM were also compared.
RESULTS
Demographic characteristics, comorbidities and ECG abnormalities were similar between controls and patients (p>0.05), except for a higher frequency of left ventricular hypertrophy (LVH) in patients (10.7% vs. 1.2%, p=0.008). Demographic characteristics, comorbidities, clinical and laboratory manifestations, were also similar between the groups PM and DM, except for the presence of cutaneous lesions only in DM. One-third of the patients had ECG abnormalities, which were more prevalent in PM than DM (50% vs. 24.4%, p=0.008). LVH, left atrial enlargement, rhythm and conduction abnormalities were more frequent in PM than DM (p<0.05 for all), especially the left anterior fascicular block.
CONCLUSIONS
We showed distinct ECG changes between DM and PM and a higher frequency of LVH in patients compared to controls. Investigation of cardiac involvement should be considered even in asymptomatic patients, especially PM. Further studies are necessary in order to determine the correlation of ECG findings with other complementary tests, clinical manifestations, disease activity and progression to other cardiac diseases.
Topics: Case-Control Studies; Cross-Sectional Studies; Dermatomyositis; Electrocardiography; Heart; Humans; Polymyositis
PubMed: 27267520
DOI: 10.1016/j.rbre.2014.08.012 -
Internal Medicine (Tokyo, Japan) Jan 2022
Topics: Autoantibodies; Dermatomyositis; Histiocytic Sarcoma; Humans; Neoplasms
PubMed: 34248123
DOI: 10.2169/internalmedicine.7995-21