-
Clinical Rheumatology Feb 2017This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their...
This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their association with cancer. Sera from 40 patients with polymyositis, dermatomyositis, and controls were tested by protein and RNA immunoprecipitation to detect autoantibodies, and immunoprecipitation-Western blot was used for anti-MJ/NXP-2, anti-MDA5, and anti-TIF1γ/α identification. Medical records were re-evaluated with specific focus on cancer. Anti-MJ/NXP-2 and anti-TIF1γ/α were the most common antibodies in dermatomyositis. In six dermatomyositis cases, we found five solid forms of cancer and one Hodgkin's lymphoma in long-term remission. Among patients with cancer-associated dermatomyositis, three were positive for anti-TIF1γ/α, two for anti-Mi-2, and one for anti-MJ/NXP-2. The strongest positivity of anti-TIF1γ was seen in two active forms of cancer, and this antibody was either negative or positive at low titers in the absence of cancer or in the 7-year remission Hodgkin's lymphoma. Four out of twenty (20 %) patients with polymyositis had solid cancer, but no specific association with autoantibodies was identified; further, none of the four cases of antisynthetase syndrome had a history of cancer. No serum myositis-associated autoantibody was observed in control sera, resulting in positive predictive value 75 %, negative predictive value 78.5 %, sensitivity 50 %, specificity 92 %, and area under the ROC curve 0.7083 for the risk of paraneoplastic DM in anti-TIF1γ/α (+) patients. Myositis-specific autoantibodies can be identified thanks to the use of immunoprecipitation, and their association with cancer is particularly clear for anti-TIF1γ/α in dermatomyositis. This association should be evaluated in a prospective study by immunoprecipitation in clinical practice.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Biomarkers; Cohort Studies; Dermatomyositis; Female; Humans; Immunoprecipitation; Inflammation; Italy; Male; Middle Aged; Myositis; Neoplasms; Polymyositis; Predictive Value of Tests; RNA; ROC Curve; Risk; Young Adult
PubMed: 27761751
DOI: 10.1007/s10067-016-3453-0 -
Journal of Medical Economics Jul 2016Background Dermatomyositis and polymyositis (DM/PM) are inflammatory myopathies characterized by muscle inflammation/weakness. Patients with DM/PM have a reduced...
Background Dermatomyositis and polymyositis (DM/PM) are inflammatory myopathies characterized by muscle inflammation/weakness. Patients with DM/PM have a reduced quality-of-life and are at an increased risk for several comorbidities. Studies have assessed the incidence and prevalence of DM/PM; however, no study has estimated the burden of the diseases in terms of both healthcare resource utilization (HCRU) and work loss incurred by patients. Objective To provide a comprehensive, current estimate of the annual HCRU and work loss in DM/PM patients in the US. Methods All patients (aged 18-64 years) with a first diagnosis of DM/PM between January 1, 1998 and March 31, 2014 ('index date') were selected from a de-identified privately-insured administrative claims database. DM/PM patients were required to have continuous health-plan enrollment 12 months prior to and following their index date. Propensity-score (1:1) matching of DM/PM patients with non-DM/PM controls was carried out based on a logistic regression of demographic characteristics, comorbidities, costs, and HCRU to control for these confounding factors. Burden of HCRU and work loss (disability days and medically-related absenteeism) were compared between the matched DM/PM and the non-DM/PM cohorts over the 12-month period after the index date ('outcome period'). Results Of the 2617 DM/PM patients that met sample selection criteria, 2587 (98.9%) were matched with a non-DM/PM control. During the outcome period, DM/PM patients had significantly increased HCRU across places of service, including 44% more inpatient admissions (3.6 vs 2.5, p < 0.001), increased visits with specialists such as rheumatologists, neurologists and physical therapists, and filled 4.7 more prescriptions (32.2 vs 27.5, p < 0.001) than matched control patients. The increased HCRU led to significantly more medically-related work loss among DM/PM patients than matched controls (p < 0.001). Conclusions DM/PM imposes a substantial increase in healthcare resource use and is associated with statistically significantly greater work loss in the first year following diagnosis.
Topics: Absenteeism; Adolescent; Adult; Comorbidity; Cost of Illness; Dermatomyositis; Female; Health Services; Humans; Insurance Claim Review; Insurance, Health; Logistic Models; Male; Middle Aged; Polymyositis; Private Sector; Propensity Score; Socioeconomic Factors; Young Adult
PubMed: 26850074
DOI: 10.3111/13696998.2016.1151433 -
Frontiers in Immunology 2022Polymyositis (PM) is an acquirable muscle disease with proximal muscle involvement of the extremities as the main manifestation; it is a category of idiopathic...
BACKGROUND
Polymyositis (PM) is an acquirable muscle disease with proximal muscle involvement of the extremities as the main manifestation; it is a category of idiopathic inflammatory myopathy. This study aimed to identify the key biomarkers of PM, while elucidating PM-associated immune cell infiltration and immune-related pathways.
METHODS
The gene microarray data related to PM were downloaded from the Gene Expression Omnibus database. The analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks were performed on differentially expressed genes (DEGs). The hub genes of PM were identified using weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) algorithm, and the diagnostic accuracy of hub markers for PM was assessed using the receiver operating characteristic curve. In addition, the level of infiltration of 28 immune cells in PM and their interrelationship with hub genes were analyzed using single-sample GSEA.
RESULTS
A total of 420 DEGs were identified. The biological functions and signaling pathways closely associated with PM were inflammatory and immune processes. A series of four expression modules were obtained by WGCNA analysis, with the turquoise module having the highest correlation with PM; 196 crossover genes were obtained by combining DEGs. Subsequently, six hub genes were finally identified as the potential biomarkers of PM using LASSO algorithm and validation set verification analysis. In the immune cell infiltration analysis, the infiltration of T lymphocytes and subpopulations, dendritic cells, macrophages, and natural killer cells was more significant in the PM.
CONCLUSION
We identified the hub genes closely related to PM using WGCNA combined with LASSO algorithm, which helped clarify the molecular mechanism of PM development and might have great significance for finding new immunotherapeutic targets, and disease prevention and treatment.
Topics: Biomarkers; Computational Biology; Gene Ontology; Gene Regulatory Networks; Humans; Polymyositis
PubMed: 36225941
DOI: 10.3389/fimmu.2022.1002500 -
Drug Research Nov 2015
Topics: Dermatomyositis; Humans; Myositis; Myositis, Inclusion Body; Polymyositis
PubMed: 26536184
DOI: 10.1055/s-0035-1558068 -
Neurotherapeutics : the Journal of the... Oct 2008Idiopathic inflammatory myopathies (notably polymyositis and dermatomyositis) are relatively uncommon diseases with a heterogeneous clinical presentation. Only a few... (Review)
Review
Idiopathic inflammatory myopathies (notably polymyositis and dermatomyositis) are relatively uncommon diseases with a heterogeneous clinical presentation. Only a few randomized, double-blind, placebo-controlled trials have been performed, measures to assess outcome and response to treatment have to be validated. Initial treatment options of first choice are corticosteroids, although rarely tested in randomized, controlled trials. Unfortunately, not all patients respond to them and many develop undesirable side effects. Thus, second line agents or immunosuppressants given in combination with corticosteroids are used. For dermatomyositis/polymyositis, combination with azathioprine is most common. In case this combination is not sufficient or applicable, intravenous immunoglobulins are justified. Alternative or stronger immunosuppressants, such as cyclosporine A, cyclophosphamide, methotrexate, or mycophenolate are also used. There are no defined guidelines or best treatment protocols agreed on internationally; therefore, the medical approach must be individualized based on the severity of clinical presentation, disease duration, presence of extramuscular features, and prior therapy and contraindications to particular agents. Approximately 25% of patients are nonresponders and continue to experience clinical relapses. Those are candidates for alternative treatment options and experimental therapies. New immunoselective therapies directed toward cytokine modulation, immune cell migration, or modification of certain immune subsets (B- and T-cells) are a promising avenue of research and clinical application. Possible future therapeutic options are presented and discussed.
Topics: Animals; Anti-Inflammatory Agents; Dermatomyositis; Humans; Myositis; Myositis, Inclusion Body; Polymyositis
PubMed: 19019306
DOI: 10.1016/j.nurt.2008.08.008 -
Medicine Aug 2018This study aims to explore the roles of cysteine-rich protein 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN2) and vascular endothelial growth factor (VEGF)... (Observational Study)
Observational Study
This study aims to explore the roles of cysteine-rich protein 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN2) and vascular endothelial growth factor (VEGF) in the vascular process of polymyositis (PM)/dermatomyositis (DM).Real-time quantitative polymerase chain reaction was used to determine the mRNA expression of Cyr61, CTGF, and VEGF in muscle tissues of initially treated PM/DM patients and controls. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of Cyr61, CTGF, and VEGF of initially treated PM/DM patients before and after treatment. Data were statistically analyzed using statistical software SPSS 17.0.The mRNA expression levels of Cyr61, CTGF, and VEGF in muscle tissues were higher in the PM and DM groups than in the control group (P < .05). Differences in the mRNA expression levels of Cyr61, CTGF, and VEGF in muscle tissues between the PM and DM groups were not statistically significant (P > .05). Before treatment, the serum levels of Cyr61, CTGF, and VEGF were higher in the PM and DM groups than in the control group (P < .05). Furthermore, in the PM and DM groups, the expression levels of Cyr61, CTGF, and VEGF in serum at 6 months after treatment were lower than those before treatment (P < .05).Cyr61, CTGF, and VEGF are involved in the pathogenesis of PM/DM. These may be involved in the pathogenesis mainly by affecting the formation of blood vessels and promoting inflammatory response. This suggests that microvascular lesions play an important role in the immune pathogenesis of inflammatory myopathy PM/DM.
Topics: Adult; Aged; Connective Tissue Growth Factor; Cysteine-Rich Protein 61; Dermatomyositis; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymyositis; Up-Regulation; Vascular Endothelial Growth Factor A; Young Adult
PubMed: 30142763
DOI: 10.1097/MD.0000000000011775 -
Arthritis Research & Therapy 2010Recent studies suggest a mechanistic role for molecules induced by type 1 interferons in the pathogenesis of some forms of myositis. For dermatomyositis, evidence that... (Review)
Review
Recent studies suggest a mechanistic role for molecules induced by type 1 interferons in the pathogenesis of some forms of myositis. For dermatomyositis, evidence that these molecules injure myofibers seems especially strong. In the group of disorders known as polymyositis, the study of blood samples suggests a potential role. It is unknown what drives the sustained presence of type 1 interferon-inducible molecules in these diseases, as the type 1 interferons themselves have not been specifically detected along with their downstream biomarkers. Therapeutic development for blockade of IFNα is in progress aided by the identification of blood genomic biomarkers.
Topics: Biomarkers; Dermatomyositis; Diagnosis, Differential; Gene Expression Regulation; Humans; Interferon Type I; Molecular Targeted Therapy; Muscle, Skeletal; Myositis, Inclusion Body; Organ Specificity; Polymyositis; RNA, Messenger; Receptor, Interferon alpha-beta; Signal Transduction; Skin; Transcription, Genetic; Tumor Necrosis Factor-alpha
PubMed: 20392291
DOI: 10.1186/ar2885 -
Scientific Reports May 2021To develop a machine learning (ML) model that predicts disease groups or autoantibodies in patients with idiopathic inflammatory myopathies (IIMs) using muscle MRI... (Observational Study)
Observational Study
To develop a machine learning (ML) model that predicts disease groups or autoantibodies in patients with idiopathic inflammatory myopathies (IIMs) using muscle MRI radiomics features. Twenty-two patients with dermatomyositis (DM), 14 with amyopathic dermatomyositis (ADM), 19 with polymyositis (PM) and 19 with non-IIM were enrolled. Using 2D manual segmentation, 93 original features as well as 93 local binary pattern (LBP) features were extracted from MRI (short-tau inversion recovery [STIR] imaging) of proximal limb muscles. To construct and compare ML models that predict disease groups using each set of features, dimensional reductions were performed using a reproducibility analysis by inter-reader and intra-reader correlation coefficients, collinearity analysis, and the sequential feature selection (SFS) algorithm. Models were created using the linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), support vector machine (SVM), k-nearest neighbors (k-NN), random forest (RF) and multi-layer perceptron (MLP) classifiers, and validated using tenfold cross-validation repeated 100 times. We also investigated whether it was possible to construct models predicting autoantibody status. Our ML-based MRI radiomics models showed the potential to distinguish between PM, DM, and ADM. Models using LBP features provided better results, with macro-average AUC values of 0.767 and 0.714, accuracy of 61.2 and 61.4%, and macro-average recall of 61.9 and 59.8%, in the LDA and k-NN classifiers, respectively. In contrast, the accuracies of radiomics models distinguishing between non-IIM and IIM disease groups were low. A subgroup analysis showed that classification models for anti-Jo-1 and anti-ARS antibodies provided AUC values of 0.646-0.853 and 0.692-0.792, with accuracy of 71.5-81.0 and 65.8-78.3%, respectively. ML-based TA of muscle MRI may be used to predict disease groups or the autoantibody status in patients with IIM and is useful in non-invasive assessments of disease mechanisms.
Topics: Adult; Aged; Antibodies, Antinuclear; Antigens, Ly; Biopsy; Dermatomyositis; Diagnosis, Differential; Female; Humans; Image Interpretation, Computer-Assisted; Machine Learning; Magnetic Resonance Imaging; Male; Middle Aged; Muscles; Polymyositis; ROC Curve; Reproducibility of Results; Retrospective Studies; Urokinase-Type Plasminogen Activator
PubMed: 33972636
DOI: 10.1038/s41598-021-89311-3 -
Chinese Medical Journal Sep 2017The immunopathologic mechanism underlying dermatomyositis (DM) and polymyositis (PM) remains poorly understood. Many cytokines play a pathogenic role in DM and PM....
BACKGROUND
The immunopathologic mechanism underlying dermatomyositis (DM) and polymyositis (PM) remains poorly understood. Many cytokines play a pathogenic role in DM and PM. Interleukin 21 (IL-21) has a pleiotropic effect on inflammation regulation. This study aimed to detect the serum IL-21 level and investigate the expression of IL-21 and IL-21 receptor (IL-21R) in muscle tissues of patients with DM and PM.
METHODS
Biopsied muscle samples were obtained from 11 patients with DM, 12 with PM, and six controls; mRNA levels of IL-21 and IL-21R were analyzed by real-time quantitative reverse transcription-polymerase chain reaction; and immunohistochemical staining was used to evaluate the protein expression of IL-21 and IL-21R. Serum samples were obtained from 36 patients with DM, 19 with PM, and 20 healthy controls. The serum IL-21 level was detected by enzyme-linked immunosorbent assay.
RESULTS
The expression of IL-21 was upregulated in patients with DM and PM. The IL-21 mRNA level was significantly increased in muscle tissues of patients with DM and PM (DM vs. control, P= 0.001; PM vs. control, P= 0.001), whereas IL-21R mRNA level in patients with DM/PM was not statistically different from that of healthy controls. Immunohistochemical staining showed both IL-21 and IL-21R were significantly expressed in the inflammatory cells in muscle tissues of patients with DM and PM. The serum IL-21 level was also significantly higher in patients with DM/PM than in controls (DM vs. control, 49.12 [45.28, 60.07] pg/ml vs. 42.54 [38.69, 48.85] pg/ml, P= 0.001; PM vs. control, 50.77 [44.19, 60.62] pg/ml vs. 42.54 [38.69, 48.85] pg/ml, P= 0.005).
CONCLUSIONS
IL-21 expression is upregulated in patients with DM and PM in both muscle tissue and serum. In addition, IL-21R protein is highly expressed in affected muscle tissues of patients with DM and PM. IL-21 may play a pathogenic role through IL-21R in patients with DM and PM.
Topics: Adult; Aged; Dermatomyositis; Female; Humans; Immunohistochemistry; Interleukins; Male; Middle Aged; Muscles; Polymyositis; RNA, Messenger; Receptors, Interleukin-21; Retrospective Studies
PubMed: 28836555
DOI: 10.4103/0366-6999.213419 -
Journal of Korean Medical Science Dec 2004A 55 yr-old man presented with progressive muscle weakness and oliguria for 5 days. Laboratory findings suggested rhabdomyolysis complicated with acute renal failure. A... (Clinical Trial)
Clinical Trial
A 55 yr-old man presented with progressive muscle weakness and oliguria for 5 days. Laboratory findings suggested rhabdomyolysis complicated with acute renal failure. A diagnosis of polymyositis was based upon the proximal muscle weakness on both upper and lower limbs, elevated muscle enzyme levels, muscle biopsy findings and the needle electromyography findings. The muscle biopsy showed extensive muscle necrosis and calcification. Investigations for underlying malignancy demonstrated hepatocellular carcinoma. The patient was managed with hemodialysis and high dose prednisolone. His renal function was fully recovered and his muscle power did improve slightly, but he died of a rupture of the hepatic tumor. In our view, this is an interesting case in that the hepatocellular carcinoma was associated with polymyositis and fulminant rhabdomyolysis-induced acute renal failure requiring hemodialysis.
Topics: Acute Kidney Injury; Carcinoma, Hepatocellular; Diagnosis, Differential; Humans; Liver Neoplasms; Male; Middle Aged; Polymyositis; Rhabdomyolysis
PubMed: 15608404
DOI: 10.3346/jkms.2004.19.6.891