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AIMS: Growth differentiation factor 15 (GDF15) plays an important role in multiple inflammatory disorders. We aimed to analyze serum GDF15 levels in adult patients with idiopathic inflammatory myopathies (IIMs). METHODS: Serum GDF15 levels were measured in 179 adult patients with IIMs and 76 healthy controls (HCs). The association between GDF15 levels and disease variables was analyzed using Spearman's rank correlation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory ability of GDF15 and the GDF15-to-lymphocyte ratio (GLR). Machine learning methods were applied to build predictive models. RESULTS: GDF15 levels and GLR were significantly elevated in patients with adult IIMs than in HCs. Compared with patients in remission, both GDF15 and GLR were significantly higher in myositis patients in an active phase. GDF15 levels correlated positively with myositis disease activity indices and negatively correlated with lymphocyte and platelet counts. ROC curve analysis revealed that GDF15 levels and GLR outperformed muscle enzymes and distinguished well between patients with active disease and those in remission. Furthermore, even in the normal muscle enzyme group, GDF15 levels and GLR were also well-distinguished between patients with active disease and those in remission. Using machine learning, a logistic regression model of GDF15 combined with creatine kinase and lymphocyte count was constructed and had a reliable predictive value for disease activity. CONCLUSIONS: GDF15, particularly GLR, was significantly correlated with disease activity in adult patients with IIMs. They could serve as useful biochemical markers for evaluating disease activity, monitoring disease progression, and guiding treatment in adult patients with IIMs.
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Systemic autoimmune diseases are complex conditions characterized by an immune system dysregulation and an aberrant activation against self-antigens, leading to tissue and organ damage. Even though genetic predisposition plays a role, it cannot fully explain the onset of these diseases, highlighting the significant impact of non-heritable influences such as environment, hormones and infections. The exposome represents all those factors, ranging from chemical pollutants and dietary components to psychological stressors and infectious agents. Epigenetics, which studies changes in gene expression without altering the DNA sequence, is a crucial link between exposome and the development of autoimmune diseases. Key epigenetic mechanisms include DNA methylation, histone modifications, and non-coding RNAs. These epigenetic modifications could provide a potential piece of the puzzle in understanding systemic autoimmune diseases and their connection with the exposome. In this work we have collected the most important and recent evidence in epigenetic changes linked to systemic autoimmune diseases (systemic lupus erythematosus, idiopathic inflammatory myopathies, ANCA-associated vasculitis, and rheumatoid arthritis), emphasizing the roles these changes may play in disease pathogenesis, their potential as diagnostic biomarkers and their prospective in the development of targeted therapies.
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Mitochondria form a dynamic network within skeletal muscle. This network is not only responsible for producing adenine triphosphate through oxidative phosphorylation, but also responds through fission, fusion and mitophagy to various factors, such as increased energy demands, oxidative stress, inflammation, and calcium dysregulation. Mitochondrial dysfunction in skeletal muscle not only occurs in primary mitochondrial myopathies, but also other hereditary and acquired myopathies. As such, this review attempts to highlight the clinical and histopathologic aspects of mitochondrial dysfunction seen in hereditary and acquired myopathies, as well as discuss potential mechanisms leading to mitochondrial dysfunction and therapies to restore mitochondrial function.
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PURPOSE: Primary biliary cirrhosis-idiopathic inflammatory myopathy (PBC-IIM) overlap syndrome (OS) is a rare condition in which cardiac involvement is observed. We aimed to characterize the clinical features and associated factors of PBC-IIM OS patients with cardiac involvement. METHODS: Patients with PBC-IIM OS that visited our hospital from January 1983 to December 2021 were enrolled. Clinical presentations and laboratory and imaging data were recorded. The clinical data of patients with and without cardiac involvement were compared. According to the first instance of a disease flare, prognostic factors were also studied. RESULTS: Thirty-four patients with PBC-IIM OS were enrolled. A total of 58.8% of patients presented with muscle weakness at disease onset, which primarily involved skeletal muscle (85.3%). Slight liver dysfunction was discovered in this OS cohort. In patients with cardiac involvement, palpitation (63.6%) and dyspnea (36.4%) were the most common onset symptoms. Arrhythmia was a vital manifestation in OS patients, in which half of OS patients had nonsustained ventricular tachycardia (50.0%, 11/22). Compared with noncardiac involvement, myalgia (4.5%, P=0.004) and fever (0.0%, P=0.011) were reported relatively rarely at disease onset in the group with cardiac involvement. The prognosis analysis showed that positivity for anti-Ro52 (HR=0.00, P=0.034) negatively correlated with relapse in OS patients. CONCLUSION: PBC-IIM OS has unique features. Typical clinical manifestations and early worsening cardiac indicators can be used to identify cardiac involvement and predict prognosis. Anti-Ro52 may have prognostic value for PBC-IIM OS.
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The co-occurrence of genetic myopathies with myasthenia gravis (MG) is extremely rare, however a few studies have been reported. We aim to explore the link between genetically inherited muscle disorders and immune-mediated neuromuscular junction conditions, taking into account the diagnostic and therapeutic implications posed by these combined conditions. We searched all English medical papers registered in Web of Knowledge, PubMed, Google Scholar, and Science Direct between January 1987 concerning the association between muscular dystrophies (MD) and MG, also adding three new cases to the series reported so far. Three new clinical cases in which MG concurs with oculopharyngeal muscular dystrophy (OPMD) or facioscapulohumeral muscular dystrophy (FSHD) or myotonic dystrophy type 2 (DM2) were reported. A comprehensive literature review showed that FSHD is the dystrophy most frequently associated with generalized MG. The AChR antibody titer is high and neurophysiologic tests prove to be an essential tool for the diagnosis. The association between MG and MD is rare but should not be underestimated. The presence of unusual clinical features suggest investigating additional overlapping condition, especially when a treatable disease like MG is suspected.
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BACKGROUND: The increased availability of myositis autoantibodies represents new possibilities and challenges in clinical practice (Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76:1955-64. https://doi.org/10.1136/annrheumdis-2017-211468 .). The aim of this study was to perform a retrospective data analysis of patient cases with positive myositis autoantibodies to analyse their significance in routine rheumatology practice. METHODS: A monocentric analysis of all the orders used to determine myositis autoantibodies from July 2019 to May 2022 in the Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany, was carried out. RESULTS: In the defined time interval, a total of 71,597 laboratory values for the antibodies mentioned above were obtained. A total of 238 different positive autoantibodies ââwere detected in 209 patients. Idiopathic inflammatory myopathy was diagnosed in 37 patients (18%), and inflammatory rheumatic diseases other than idiopathic inflammatory myopathy were diagnosed in 90 patients (43%). No inflammatory rheumatic disease was diagnosed in 82 patients (39%). General clusters of clinical manifestations were observed. CONCLUSIONS: In our cohort, we were able to show that a relevant proportion of patients with positive myositis antibodies did not have idiopathic inflammatory myopathies or inflammatory rheumatic diseases. This finding indicates the importance of myositis autoantibodies in this group of patients. However, further studies on the course of symptoms and examination results in patients without inflammatory rheumatic diseases and with positive myositis antibodies are necessary.
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Autoanticorpos , Miosite , Reumatologia , Humanos , Miosite/imunologia , Miosite/sangue , Miosite/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Autoanticorpos/imunologia , Autoanticorpos/sangue , Pessoa de Meia-Idade , Adulto , Idoso , Doenças Reumáticas/imunologia , Doenças Reumáticas/diagnóstico , Adulto Jovem , Relevância ClínicaRESUMO
There is a well-established relationship between different subsets of idiopathic inflammatory myopathies (IIMs, myositis) and interstitial lung disease (ILD), with lung complications sometimes presenting prior to myopathic manifestations. The subtypes of myositis include those that are strongly associated with ILD, such as polymyositis (PM) and dermatomyositis (DM). Research has shown that in certain patients, these can then be further divided into subtypes using myositis-specific antibodies (MSAs), which are specific for myositis, and myositis-associated antibodies (MAAs), which can be found in myositis in overlap syndromes with other connective tissue diseases (CTDs). Notably, certain MSAs and MAAs are associated with ILD in patients with myositis. The clinical presentations of ILD in patients with myositis can vary widely and can be insidious in onset and difficult to diagnose. As ILD can progress rapidly in some cases, it is essential that clinicians are able to identify and diagnose ILD in patients with myositis. For this reason, the aim of this review is to highlight the clinical features, diagnostic criteria, important histopathologic, laboratory, and radiographic features, and treatment modalities for those patients with myositis-associated ILD.
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No published studies have investigated the correlation between religiosity, spirituality, mental health, and idiopathic inflammatory myopathy (IIM) or systemic autoimmune myopathy. Therefore, we aimed to evaluate the association between religiosity/spirituality, sociodemographic factors, and the mental health of IIM patients. This is a multicenter case-control study that included 151 patients with IIMs and 95 individuals without autoimmune diseases (controls), held between August 2022 and April 2023. This study used a semi-structured questionnaire that included sociodemographic information and the juxtaposition of the following questionnaires: the Attitudes Related to Spirituality Scale (ARES); the Duke University Religion Index (DUKE), which is composed of the organizational religious affiliation (ORA), non-organizational religious affiliation (NORA), and intrinsic religiosity (IR) domains; and the General Health Questionnaire-12 (GHQ-12). Data were analyzed using Epi Info software 7.2.5 (Centers for Disease Control and Prevention, Atlanta, GA, USA). A comparison between the mean values of the ARES, DUKE, and GHQ-12 scales was made using the Wilcoxon-Mann-Whitney and Kruskal-Wallis tests. A logistic regression test was used with the variables whose difference was statistically significant in the univariate analysis. Correlation analysis was performed using the Spearman rho coefficient. A higher prevalence of evangelicals and a lower prevalence of Catholics (p < 0.050) were seen in the IIM group compared to controls. Positive association was demonstrated between IIMs and the pardo ethnicity (OR = 2.26, 95% CI = 1.20-4.25, p = 0.011), highest ORA (OR = 2.81, 95% CI = 1.53-5.15, p < 0.001), NORA (OR = 3.99, 95% CI = 1.94-8·18, p < 0.001), IR (OR = 5.27, 95% CI = 2.32-11.97, p < 0.001), and ARES values (OR = 1.08, 95% CI = 1.04-1.13, p < 0.001). Mental health levels were compared between the groups (p > 0.999). Therefore, higher levels of religiosity and spirituality were observed in the IIM group than in the control group, but there was a similar distribution of mental health levels. The following can be cited as advantages of the present study: (i) the large sample for a rare disease with the presence of a control group; (ii) the multicenter characteristic with participation from three regions of Brazil; (iii) being the first study to map aspects of religiosity, spirituality, and mental health in IIMs.
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Saúde Mental , Religião , Espiritualidade , Humanos , Estudos de Casos e Controles , Masculino , Feminino , Pessoa de Meia-Idade , Brasil/epidemiologia , Adulto , Miosite/psicologia , Idoso , Inquéritos e QuestionáriosRESUMO
Introduction: The objective of this study was to examine the effects of in ovo nicotinamide riboside (NR) feeding on high-yield broiler growth and meat quality. Methods: Fertilized Cobb 700 by-product eggs (N = 3,240) were randomly assigned to one of four in ovo treatments and injected with 0 (0NR), 250 (250NR), 500 (500NR), or 1,000 (1,000NR) mM NR at incubation-day 10. Chicks were hatched, vent sexed, and randomly placed 18 per pen in one of 32 floor pens. On day 48, birds were processed and deboned. Results: There were dose effects for all part weights (p < 0.05). Pectoralis major weight of 250, 500, and 1,000NR carcasses were heavier than 0NR (p < 0.03) but did not differ from remaining NR doses (p > 0.26). Pectoralis minor weight of 250NR carcasses was greater (p < 0.01) than 0NR and did not differ from other NR tenders (p > 0.21). Pectoralis minor weight of 500 and 1,000NR carcasses was greater than 0NR (p < 0.09), but did not differ (P = 0.82) from each other. There were no dose effects for all Pectoralis major and minor myopathy scores and incidence except incidence of tenders scoring "0" and "1" for woody-like tender. Percentage of NR1,000 tenders scoring 0 and 1 for woody-like tender were less than and greater than all other treatments, respectively (p < 0.05). There were no differences among remaining NR doses and NR0 tenders (p > 0.10). There were dose effects for muscle fiber number (P = 0.03). There tended to be more muscle fibers within 250 and 1,000NR muscles compared to 0NR (p < 0.09). Pectoralis major muscle from 500NR did not differ in muscle fiber number compared to 250 and 1,000NR (p > 0.18), but had more (p < 0.01) fibers than 0NR muscle. There tended to be more fibers in 250 and 1,000NR muscles compared to 0NR muscle (p < 0.09). Discussion: Nicotinamide riboside in ovo feeding caused birds to produce heavier parts; however, myopathy scores and incidence were minimally affected which may have been due greater muscle fiber number.
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Background: Acute exacerbation of idiopathic inflammatory myopathies-associated interstitial lung disease (AE-IIM-ILD) is a significant event associated with increased morbidity and mortality. However, few studies investigated the potential prognostic factors contributing to mortality in patients who experience AE-IIM-ILD. Objectives: The purpose of our study was to comprehensively investigate whether high-resolution computed tomography (HRCT) findings predict the 1-year mortality in patients who experience AE-IIM-ILD. Methods: A cohort of 69 patients with AE-IIM-ILD was retrospectively created. The cohort was 79.7 % female, with a mean age of 50.7. Several HRCT features, including total interstitial lung disease extent (TIDE), distribution patterns, and radiologic ILD patterns, were assessed. A directed acyclic graph (DAG) was used to evaluate the statistical relationship between variables. The Cox regression method was performed to identify potential prognostic factors associated with mortality. Results: The HRCT findings significantly associated with AE-IIM-ILD mortality include TIDE (HR per 10%-increase, 1.64; 95%CI, 1.29-2.1, p < 0.001; model 1: C-index, 0.785), diffuse distribution pattern (HR, 3.75, 95%CI, 1.5-9.38, p = 0.005; model 2: C-index, 0.737), and radiologic diffuse alveolar damage (DAD) pattern (HR, 6.37, 95 % CI, 0.81-50.21, p = 0.079; model 3: C-index, 0.735). TIDE greater than 58.33 %, diffuse distribution pattern, and radiologic DAD pattern correlate with poor prognosis. The 90-day, 180-day, and 1-year survival rates of patients who experience AE-IIM-ILD were 75.3 %, 66.3 %, and 63.3 %, respectively. Conclusion: HRCT findings, including TIDE, distribution pattern, and radiological pattern, are predictive of 1-year mortality in patients who experience AE-IIM-ILD.
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OBJECTIVE: Idiopathic inflammatory myopathies (IIM) are a heterogeneous and life-threatening group of diseases, especially anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis (MDA5+ DM) is reportedly strongly associated with high mortality rate. Tacrolimus (TAC) provides an excellent therapeutic option, but the trough concentration (Cmin) -outcome relationship remains unexplored. This study was undertaken to identify optimal Cmin and individualized dose based on CYP3A5 genotype for IIM patients. METHODS: 134 IIM patients with 467 Cmin were enrolled. We examined the relationship between TAC Cmin and relapses. The receiver operating characteristic analysis was used to confirm the optimal Cmin. Analyses of factors influencing Cmin were conducted. The dose requirement based on CYP3A5 genotype was confirmed. RESULTS: TAC Cmin is strongly associated with relapses. The optimal cutoff values were 5.30, 5.85, 4.85 and 5.35 ng/ml for acute, subacute, chronic and all phase IIM patients (p = 0.001, 0.013, 0.002, and < 0.001, respectively), as well as 5.35, 5.85, 5.55 and 5.85 ng/ml for acute, subacute, chronic and all phase MDA5+ DM patients (p = 0.007, 0.001, 0.036, and < 0.001, respectively). CYP3A5 genotype was one of the significant factors influencing TAC Cmin. CYP3A5 expressers required 0.059 mg/kg/d to attain the target Cmin, while nonexpressers required 0.046 mg/kg/d (p = 0.019). CONCLUSION: TAC treatment may elicit favorable outcome in patients with IIM and MDA5+ DM when Cmin exceeded 5.35 and 5.85 ng/ml, which is crucial to lower relapse rate. The individualized dose based on the CYP3A5 genotype provides a reference for TAC personalized therapy in IIM.
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Idiopathic inflammatory myopathies (IIM) impact all aspects of health, physiological, physical, and psychological. Hallmark symptoms of IIM are muscle weakness, reduced muscle endurance and aerobic capacity. Recently, pain and fatigue as well as anxiety and depression have emerged as common and debilitating symptoms in patients with IIM. The aim of this scoping review is to, in a holistic way, describe how IIM impact patients' physiological, physical, and psychological health and how exercise has a role to treat as well as potentially counteract the effects of the disease. Inflammation induces non-immune response and organ damage. These changes with additional impact of physical inactivity lead to muscle impairment and reduced aerobic capacity. Pain, fatigue and low psychological well-being and overall quality of life are also common health aspects of IIM. Medical treatment can reduce inflammation but has in turn serious side effects such as muscle atrophy, type-II diabetes, and hypertension, which exercise has the potential to treat, and perhaps also counteract. In addition, exercise improves muscle function, aerobic capacity and might also reduce fatigue and pain. New evidence shows that reducing systemic inflammation may also improve patient-reported subjective health, quality of life and psychological well-being. Exercise in combination with medical treatment is becoming an important part of the treatment for patients with IIM as exercise has the potential to promote health aspects of various dimensions in patients with IIM.
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BACKGROUND: The identification of idiopathic inflammatory myopathies (IIMs) requires a comprehensive analysis involving clinical manifestations and histological findings. This study aims to provide insights into the histopathological and immunohistochemical aspects of IIMs. METHODS: This retrospective case series involved 56 patients diagnosed with IIMs at the Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, from 2019 to 2023. The histology and immunohistochemical expression of HLA-ABC, HLA-DR, C5b-9, Mx1/2/3, and p62 were detected. RESULTS: We examined six categories of inflammatory myopathy, including immunemediated necrotizing myopathy (58.9%), dermatomyositis (DM; 23.2%), overlap myositis (8.9%), antisynthetase syndrome (5.4%), inclusion body myositis (IBM; 1.8%), and polymyositis (1.8%). The average age of the patients was 49.7 ± 16.1 years, with a female-to-male ratio of 3:1. Inflammatory cell infiltration in the endomysium was present in 62.5% of cases, perifascicular atrophy was found in 17.8%, and fiber necrosis was observed in 42 cases (75.0%). Rimmed vacuoles were present in 100% of cases in the IBM group. Immunohistochemistry showed the following positivity rates: HLA-ABC (89.2%), HLA-DR (19.6%), C5b-9 (57.1%), and Mx1/2/3 (10.7%). Mx1/2/3 expression was high in DM cases. p62 vacuole deposits were noted in the IBM case. The combination of membrane attack complex and major histocompatibility complex I helped detect IIMs in 96% of cases. CONCLUSIONS: The diagnosis of IIMs and their subtypes should be based on clinical features and histopathological characteristics. Immunohistochemistry plays a crucial role in the diagnosis and differentiation of these subgroups.
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An 81-year-old woman presented with statin-induced anti-HMGCR immune-mediated necrotizing myopathy. Treatment was successful without complications with a reduced oral steroid dosage from the current consensus for all ages and backgrounds. This case suggests the importance of early diagnosis and the possibility of steroid dosage adjustment considering the patient's age, disease severity, and comorbidities.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Musculares , Humanos , Feminino , Idoso de 80 Anos ou mais , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Doenças Musculares/tratamento farmacológico , Doenças Musculares/induzido quimicamente , Doenças Musculares/imunologia , Doenças Musculares/diagnóstico , Necrose , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Administração Oral , Hidroximetilglutaril-CoA Redutases/imunologiaRESUMO
Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points ⢠The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. ⢠We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. ⢠The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.
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Autoanticorpos , Doença Celíaca , Miosite , Humanos , Doença Celíaca/epidemiologia , Doença Celíaca/imunologia , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Doença Celíaca/complicações , Estudos Transversais , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Prevalência , Autoanticorpos/sangue , Miosite/imunologia , Miosite/epidemiologia , Miosite/sangue , México/epidemiologia , Transglutaminases/imunologia , Idoso , Imunoglobulina A/sangue , Gliadina/imunologia , Imunoglobulina G/sangue , Proteína 2 Glutamina gama-GlutamiltransferaseRESUMO
OBJECTIVE: To investigate the epigenetic footprint of idiopathic inflammatory myopathies (IIM) through characterization of circulating extracellular vesicles (EVs) and the expression of EV-derived small non-coding RNAs (sncRNAs). METHODS: In this cross-sectional study, EVs were isolated by size-exclusion chromatography from plasma of patients with IIM and age- and sex-matched healthy donors (HD). EV-derived sncRNAs were sequenced and quantified using Next-Generation Sequencing (NGS). Following quality control and normalization, filtered count reads were used for differential microRNA (miRNA) and piwi-interacting RNA (piRNA) expression analyses. Putative gene targets enriched for pathways implicated in IIM were analyzed. Patients' clinical and laboratory characteristics at the time of sampling were recorded. RESULTS: Forty-seven IIM patients and 45 HD were enrolled. MiR-486-5p (p < 0.01), miR-122-5p, miR-192-5p, and miR-32-5p were significantly upregulated (p < 0.05 for all), while miR-142-3p (p < 0.001), miR-141-3p (p < 0.01), let-7a-5p (p < 0.05) and miR-3613-5p (p < 0.05) downregulated in EVs from IIM patients versus HD. MiR-486-5p was associated with raised muscle enzymes levels. Several target genes of up/downregulated miRNAs in IIM participate in inflammation, necroptosis, interferon and immune signaling. Six piRNAs were significantly dysregulated in IIM EVs versus HD (p < 0.05). Within IIM, miR-335-5p was selectively upregulated and miR-27a-5p downregulated in dermatomyositis (n = 21, p < 0.01). Finally, plasma EV levels were significantly increased in cancer-associated myositis (CAM, n = 12) versus non-CAM IIM (n = 35, p = 0.02) and HD (p < 0.01). EVs cargo in CAM was significantly enriched of let-7f-5p and depleted of miR-143-3p. CONCLUSION: Through an unbiased screening of EV-derived sncRNAs, we characterize miRNAs and piRNAs in the EVs cargo as potential biomarkers and modifiers of diverse IIM phenotypes.
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Biomarcadores , Vesículas Extracelulares , MicroRNAs , Miosite , Pequeno RNA não Traduzido , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Feminino , Masculino , Pessoa de Meia-Idade , Miosite/genética , Miosite/sangue , Miosite/diagnóstico , Miosite/imunologia , Estudos Transversais , MicroRNAs/genética , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/sangue , Adulto , Idoso , Sequenciamento de Nucleotídeos em Larga Escala , Perfilação da Expressão GênicaRESUMO
Heat stress can greatly challenge growth and meat quality of broiler chickens where research is looking for sustainable ingredients, such as microalgae, that could also alleviate its negative impacts. Thus, in the present study, 576 1-D-old chicks (Ross 308) were housed until commercial slaughtering (42 D) in 36 pens in 2 rooms of a poultry house, according to a full factorial design encompassing 2 room temperatures (standard vs. high), 2 sexes (females vs. males), and 3 dietary treatments, that is, diet C0 (control diet), diet C3, and diet C6 containing 0, 3, and 6%, respectively, of C. vulgaris meal replacing the same quantities of soybean meal. The highest inclusion level of C. vulgaris decreased feed intake (P < 0.001) and body weight (P < 0.0001) compared to the control diet; it increased yellow and red indexes (P < 0.0001) of the breast muscle, besides the proportion of n3 polyunsaturated fatty acids (PUFA) (P = 0.028). Heat stress decreased feed intake (P = 0.001), breast (P = 0.001) and p. major yields (P = 0.036), and increased meat pH (P= 0.008) and cooking losses (P < 0.001), umami (P = 0.021) and brothy flavor (P < 0.001), and the proportion of n3 PUFA rates (P = 0.027), while reducing the contents of several amino acids in the breast meat (P ≤ 0.05). Compared to females, males displayed higher feed intake and growth, and more favorable feed conversion (P < 0.001). Carcass and p. major yields were greater in females (P < 0.001) which also showed a higher occurrence of spaghetti meat compared to males (P < 0.001). In conclusion, C. vulgaris can be used to replace until 3% of soybean meal in diets for broiler chickens without negative implications, while positively affecting breast meat color according to consumers' preferences. However, the microalgae inclusion did not mitigate the negative effects of a chronic heat stress on growth performance nor reduced the occurrence of any myopathies.
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Ração Animal , Galinhas , Chlorella vulgaris , Dieta , Suplementos Nutricionais , Carne , Animais , Ração Animal/análise , Galinhas/fisiologia , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Masculino , Carne/análise , Feminino , Suplementos Nutricionais/análise , Chlorella vulgaris/química , Temperatura Alta , Resposta ao Choque Térmico , Distribuição Aleatória , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacosRESUMO
In vivo, muscle and neuronal cells are post-mitotic, and their function is predominantly regulated by proteostasis, a multilayer molecular process that maintains a delicate balance of protein homeostasis. The ubiquitin-proteasome system (UPS) is a key regulator of proteostasis. A dysfunctional UPS is a hallmark of muscle ageing and is often impacted in neuromuscular disorders (NMDs). Malfunction of the UPS often results in aberrant protein accumulation which can lead to protein aggregation and/or mis-localization affecting its function. Deubiquitinating enzymes (DUBs) are key players in the UPS, controlling protein turnover and maintaining the free ubiquitin pool. Several mutations in DUB encoding genes are linked to human NMDs, such as ATXN3, OTUD7A, UCHL1 and USP14, whilst other NMDs are associated with dysregulation of DUB expression. USP5, USP9X and USP14 are implicated in synaptic transmission and remodeling at the neuromuscular junction. Mice lacking USP19 show increased maintenance of lean muscle mass. In this review, we highlight the involvement of DUBs in muscle physiology and NMDs, particularly in processes affecting muscle regeneration, degeneration and inflammation following muscle injury. DUBs have recently garnered much respect as promising drug targets, and their roles in muscle maturation, regeneration and degeneration may provide the framework for novel therapeutics to treat muscular disorders including NMDs, sarcopenia and cachexia.
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Enzimas Desubiquitinantes , Humanos , Animais , Enzimas Desubiquitinantes/metabolismo , Músculo Esquelético/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Doenças Neuromusculares/metabolismo , Doenças Neuromusculares/genética , Doenças Neuromusculares/fisiopatologia , Doenças Neuromusculares/enzimologia , Doenças Musculares/metabolismo , Doenças Musculares/genética , Camundongos , ProteostaseRESUMO
BACKGROUND: Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post-vaccination. METHODS: A cross-sectional study was conducted among participants with self-reported new-onset SAIDs using the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset-a validated, patient-reported e-survey-to analyze the long-term safety of COVID-19 vaccines. Baseline characteristics of patients with new-onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio. RESULTS: Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new-onset SAID post-vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new-onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9-9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3-5.3; p = .004). New-onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1-1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3-1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2-4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4-0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs. CONCLUSION: This study reports a low occurrence of new-onset SAIDs following COVID-19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre-existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID-19 vaccination in the general population. However, long-term studies are needed to understand the autoimmune phenomena arising post-vaccination.
Assuntos
Doenças Autoimunes , Vacinas contra COVID-19 , COVID-19 , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Vacinas contra COVID-19/efeitos adversos , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/diagnóstico , Estudos Transversais , COVID-19/prevenção & controle , COVID-19/epidemiologia , Idoso , Adulto , Vacinação/efeitos adversos , Fatores de Risco , SARS-CoV-2/imunologiaRESUMO
Idiopathic Inflammatory Myopathies are rare conditions with several heterogeneous disease subtypes. They can range from limited muscle or skin involvement to severe, systemic, life-threatening disease. Although the etiology is unknown, some evidence suggests a role for external agents, particularly drugs. Herein, we present a case of a 71-year-old woman with chronic myeloid leukemia who developed imatinib-induced dermatomyositis sine dermatitis. The presentation was predominantly muscular, characterized by proximal muscle weakness and myalgia of the lower limbs, with positive anti-Mi2a antibodies. Spontaneous recovery was observed after drug discontinuation, without the need for immunosuppressive therapy. This is the first confirmed description of an imatinib-induced dermatomyositis sine dermatitis. It reflects the importance of a high awareness from rheumatologists and hematologists to accurately anticipate and identify similar situations.