Cardiac findings in children with juvenile Dermatomyositis at disease presentation.
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ABSTRACT:
SUBMITTER: Cantez S
PROVIDER: S-EPMC5504613 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:Background :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Results: Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodeling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes--HLA-DQA1, smooth muscle myosin heavy chain, clustering, plexin D1 and tenomodulin--were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. Conclusions: We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology. Keywords: Disease progression; time course
2008-07-18 | GSE11971 | GEO
Project description:Background :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Results: Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodeling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes--HLA-DQA1, smooth muscle myosin heavy chain, clustering, plexin D1 and tenomodulin--were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. Conclusions: We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology. Experiment Overall Design: After obtaining informed consent, 23 girls with definite JDM were enrolled in this study prior to obtaining the MRI directed diagnostic muscle biopsy. All 23 JDM samples and 4 healthy age- and sex-matched controls were expression profiled and for first gene filtering. Only profiling data from untreated patients (19 profiles) were then analyzed statistically. Experiment Overall Design: disease duration : less than 2 months: YJD-JDM-2UA-s2,YJD-JDM-1UA-s2,YJD-JDM-16UA-s2 Experiment Overall Design: disease duration : more than 2 months:YJD-JDM-30UA-s2,YJD-JDM-19UA-s2,YJD-JDM-5UA-s2,YJD-JDM-21UA-s2,YJD-JDM-18UA-s2,YJD-JDM-3UA-s2,YJD-JDM-23UA-s2,YJD-JDM-9UA-S2,YJD-JDM-12UA-s2,YJD-JDM-14UA-s2,YJD-JDM-25UA-s2,YJD-JDM-8UA-s2,YJD-JDM-15UA-s2,YJD-JDM-13UA-s2,YJD-JDM-10UA-S2,YJD-JDM-6UA-s2.
2008-10-21 | E-GEOD-11971 | biostudies-arrayexpress
Project description:ObjectiveRecent advances in molecular techniques have revealed that there is bi-directional transfer of cells between mother and child during pregnancy, and the presence of a mother's cells in her child has been termed maternal microchimerism (MMc). There is the potential for maternal cells to provoke inappropriate immune responses in the child, which could be a factor in autoimmunity including JDM. The aim of this study was to determine whether maternal (female) cells could be detected in frozen muscle sections from seven males (age range 3-13 years) with JDM participating in the Juvenile Dermatomyositis National (U.K. and Ireland) Cohort Biomarker Study and Repository for Idiopathic Inflammatory Myopathies and sections of muscle controls (age range 2-12 years).MethodsAt least 1000 cells from each section underwent FISH and confocal imaging through each nucleus. Concomitant IF for CD45 was used to determine whether MMc in muscle were lymphocytes. A non-parametric Mann-Whitney U-test was used to detect statistical differences.ResultsThe frequency of MMc was higher in JDM muscle (0.42-1.14%) than in controls (0.08-0.42%) P?=?0.01. No CD45+ MMc were observed.ConclusionThese data confirm an increased frequency of MMc in JDM. More detailed characterization of MMc is required, particularly using phenotypic markers, to explain the role of these cells in JDM.
| S-EPMC3354676 | biostudies-literature
Project description:Juvenile dermatomyositis (JDM) is a rare autoimmune disease mainly characterized by muscle and skin involvement. Vasculopathy is considered central to the pathogenesis of the disease. The exact nature of vasculopathy is not yet understood but it is a complex process with both an inflammatory and a non-inflammatory, occlusive component. Impaired function of JDM vasculature includes immune complex deposition, altered expression of cell adhesion molecules predominantly inducing Th17 cell infiltration, and endothelial cell dysfunction. Development of vasculopathy is associated with the severe extra-muscular manifestations of JDM, such as gastrointestinal and cardiac manifestations, interstitial lung disease, ulcerative skin disease or development of calcinosis, and portends a poor prognosis. Correlation of histopathological findings, autoantibodies, and extensive diagnostic workup represent key elements to the early detection of vasculopathic features and early aggressive treatment. Monitoring of vasculopathy remains challenging due to the lack of non-invasive biomarkers. Current treatment approaches provide variable benefit, but better understanding of the essential pathogenic mechanisms should help lead to improved outcomes. Whilst acknowledging that evidence is limited, this review aims to describe the vasculopathy of JDM in the context of pathophysiology, clinical features, and treatment of disease.
| S-EPMC6189418 | biostudies-literature
Project description:ObjectivesJuvenile Dermatomyositis (JDM) is a rare, chronic autoimmune condition of childhood, with known psychosocial implications. In this study, we sought to establish current psychological support for children and young people across the UK with rheumatic conditions, with a specific focus on those with JDM.MethodsElectronic surveys were distributed to the 15 centres that belong to the JDM Research Group in the UK, collecting responses from health-care professionals in the fields of medicine, nursing and psychology.ResultsOne hundred per cent of professionals from medicine and nursing replied from all 15 centres. Of these, 7 (47%) did not have a named psychologist as part of their rheumatology team, despite the majority [13 (87%)] having >200 paediatric rheumatology patients. Of the remaining centres, hospital psychology provision varied considerably. When rating their service, only 3 (8%) of 40 professionals scored their service as five (where one is poor and five is excellent); there were wide discrepancies in these scores. Many challenges were discussed, including limited psychology provision, lack of time and difficulties in offering support across large geographical areas.ConclusionMany of the challenges discussed are applicable to other centres worldwide. Suggestions have been proposed that might help to improve the situation for children and young people with rheumatic conditions, including JDM. Based on these findings, we suggest that rheumatology teams maximize use of these data to advocate and work toward more comprehensive psychology provision and support in their individual centres.
| S-EPMC8522803 | biostudies-literature
Project description:ObjectiveThe aim was to assess environmental factors associated with disease flare in juvenile and adult dermatomyositis (DM).MethodsAn online survey of DM patients from the USA and Canada examined smoking, sun exposure, infections, medications, vaccines, stressful life events and physical activity during the 6 months before flares, or in the past 6 months in patients without flares. Differences were evaluated by χ 2 and Fisher's exact tests, and significant univariable results were examined in multivariable logistic regression. Residential locations before flare were correlated with the National Weather Service UV index.ResultsOf 210 participants (164 juvenile and 46 adult DM), 134 (63.8%) experienced a disease flare within 2 years of the survey. Subjects more often reported disease flare after sun exposure [odds ratio (OR) = 2.0, P = 0.03], although use of photoprotective measures did not differ between those with and without flare. Urinary tract infections (OR = 16.4, P = 0.005) and gastroenteritis (OR = 3.2, P = 0.04) were more frequent in the preceding 6 months in those who flared. Subjects who flared recently used NSAIDS (OR = 3.0, P = 0.0003), blood pressure medicines (OR = 3.5, P = 0.049) or medication for depression or mood changes (OR = 12.9, P = 0.015). Moving to a new house (OR = 10.3, P = 0.053) was more common in those who flared. Only sun exposure (OR = 2.2) and NSAIDs (OR = 1.9) were significant factors in multivariable analysis.ConclusionCertain classes of environmental agents that have been associated with the initiation of DM, including sun exposure and medications, may also play a role in disease flares.
| S-EPMC5850835 | biostudies-literature
Project description:ObjectivesWe aimed to develop and assess the reliability of a novel MRI-based scoring system for reporting the severity of MRI findings in children with suspected JDM.MethodsNine consultant paediatric radiologists independently assessed and scored 40 axial and 30 coronal thigh MR images of children with suspected JDM on two occasions using the juvenile dermatomyositis magnetic resonance Imaging Score (JIS). JIS was calculated for both reads for each plane and each limb, with possible scores ranging from 0 (normal) to 100 (severe). Inter- and intraobserver agreement was calculated using the intraclass correlation coefficient (ICC) and two- and one-way random effects models, respectively. Bland-Altman plots of the difference in JIS against the average JIS were also produced for each rater.ResultsOverall, the interobserver reliability and agreement was good-for axial images, JIS ranged from 46.8 to 61.0 [ICC = 0.88 (95% CI: 0.82, 0.92)] for the left limb and 47.9-61.4 [ICC = 0.87 (95% CI: 0.81, 0.92)] for the right limb. For coronal images, JIS ranged from 56.7 to 65.1 [ICC = 0.90 (95% CI: 0.85, 0.95)] for the left limb and 55.7 to 66.8 [ICC = 0.90 (95% CI: 0.84, 0.94)] for the right limb. The intraobserver reliability and agreement was good, with ICC ranging from 0.90 to 0.94.ConclusionJIS is a semi-objective scoring system with potential to serve as a reliable biomarker of disease severity and response to therapeutic interventions in children with JDM.
| S-EPMC6105921 | biostudies-literature
Project description:ObjectiveJuvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis-specific autoantibodies (MSAs) have prognostic significance in juvenile DM.MethodsMuscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow-up 4.9 years). Long-term treatment status (on or off medication over time) was modeled using generalized estimating equations.ResultsMuscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48-fold higher odds (95% confidence interval [95% CI] 1.12-1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10-fold higher odds (95% CI 1.01-1.21; P = 0.038). A protective effect was identified in patients with anti-Mi-2 autoantibodies, in whom the odds of remaining on treatment were 7.06-fold lower (95% CI 1.41-35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti-nuclear matrix protein 2 autoantibodies, anti-transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61-fold higher odds (95% CI 1.16-2.22; P = 0.004), and for the total biopsy score, 1.13-fold higher odds (95% CI 1.03-1.24; P = 0.013).ConclusionHistopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease.
| S-EPMC5091622 | biostudies-literature
Project description:In this study, we determined if B lymphocytosis may serve as a JDM biomarker for disease activity. Children with untreated JDM were divided into two groups based on age-adjusted B cell percentage (determined through flow cytometry): 90 JDM in the normal B cell group and 45 in the high B cell group. We compared through T-testing the age, sex, ethnicity, duration of untreated disease (DUD), disease activity scores for skin (sDAS), muscle (mDAS), total (tDAS), CMAS, and neopterin between these two groups. The patients in the high B cell group had a higher tDAS (p = 0.009), mDAS (p = 0.021), and neopterin (p = 0.0365). Secondary analyses included B cell values over time and BAFF levels in matched patients with JM (juvenile myositis) and concurrent interstitial lung disease (ILD); JM alone and healthy controls Patient B cell percentage and number was significantly higher after 3-6 months of therapy and then significantly lower on completion of therapy (p =< 0.0001). The JM groups had higher BAFF levels than controls 1304 vs. 692 ng/mL (p = 0.0124). This study supports B cell lymphocytosis as a JDM disease-activity biomarker and bolsters the basis for B cell-directed therapies in JDM.
| S-EPMC10453137 | biostudies-literature
Project description:Objective To determine the short-term effectiveness safety of baricitinib in children with refractory and/or severe juvenile dermatomyositis (rsJDM) in a real-world setting. Methods This was a single-center retrospective study, including 20 children with rsJDM. They were all treated using baricitinib combined with steroids and other immunosuppressive agents. The childhood myositis assessment scale (CMAS) and PRINTO remission criteria were used to evaluate the disease severity and treatment outcome at 0, 4, 12, and 24 weeks after initiation of baricitinib. Results The skin rash improved in 95% of patients (19/20) at week 24, with a significant decrease of skin-DAS at weeks 12 (6.0 vs. 2.0, p < 0.05] and week 24 [6.0 vs. 1.0, p < 0.05) by median statistics. The CMAS score increased significantly at week 12 (41.0 [29.0, 44.0] vs. 46.0 [42.0, 52.0], p < 0.05) and week 24 (41.0 [29.0, 44.0] vs. 50.0 [45.0, 52.0], p < 0.05), as did the manual muscle testing (MMT)-8 score at week 24 (73.0 [610, 76.0] vs. 79.0 [77.0, 80.0], p < 0.05). At 24 weeks, the complete response (CR) and partial response (PR) were achieved in 75% (15/20) and 15% (3/20), respectively. The dose of corticosteroids (CS) decreased by 37% from the baseline (0.53 [0.42, 1.00] mg/kg) to week 12 (0.33 [0.18, 0.40] mg/kg) (p < 0.05), and by 49% at week 24 (p < 0.05). No serious side effects were observed. Conclusion Baricitinib combined with traditional immunosuppressants treatment was efficacious in rsJDM. Add-on therapy of baricitinib was helpful for tapering CS dose. No serious side effects were observed in this study.
| S-EPMC9530147 | biostudies-literature