Meta-analyses uncover the genetic architecture of Idiopathic Inflammatory Myopathies.

Objective: Idiopathic inflammatory myopathies (myositis, IIMs) are rare, systemic autoimmune disorders that lead to muscle inflammation, weakness, and extra-muscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis dataset to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.

Changes in Confidence, Feelings, and Perceived Necessity Concerning COVID-19 Booster.

The COVID-19 booster first became available to all adults in the U.S. in November 2021 and a bivalent version in September 2022, but a large population remains booster-hesitant; only 17% of Americans have obtained the updated vaccine as of June 2023.

Performance of the 2016 ACR-EULAR myositis response criteria in juvenile dermatomyositis therapeutic trials and consensus profiles.

Objectives: The 2016 ACR-EULAR Response Criteria for JDM was developed as a composite measure with differential weights of six core set measures (CSMs) to calculate a Total Improvement Score (TIS). We assessed the contribution of each CSM, representation of muscle-related and patient-reported CSMs towards improvement, and frequency of CSM worsening across myositis response criteria (MRC) categories in validation of MRC.

Methods: Data from JDM patients in the Rituximab in Myositis trial (n = 48), PRINTO JDM trial (n = 139), and consensus patient profiles (n = 273) were included.

Academic Careers in Advocacy: Aligning Institutional Values Through Use of an Advocacy Portfolio.

Academic children's hospitals must embrace advocacy as a central component of their missions to discover new knowledge and improve the health of the communities and patients they serve. To do so, they must ensure faculty have both the tools and the opportunities to develop and articulate the work of advocacy as an academic endeavor. This can be accomplished by integrating the work of advocacy at the community and policy-change levels into the traditional value systems of academic medicine, especially the promotions process, to establish its legitimacy.

Gene Expression Profiles of Treatment Response and Non-Response in Children With Juvenile Dermatomyositis.

Objective: The study objective was to identify differences in gene expression between treatment responders (TRs) and treatment non-responders (TNRs) diagnosed with juvenile dermatomyositis (JDM).

Methods: Gene expression analyses were performed using whole blood messenger RNA sequencing in patients with JDM (n = 17) and healthy controls (HCs; n = 10). Four analyses were performed (A1-4) comparing differential gene expression and pathways analysis exploiting the timing of sample acquisition and the treatments received to perform these comparative analyses.

Association with HLA-DRβ1 position 37 distinguishes juvenile dermatomyositis from adult-onset myositis.

Juvenile dermatomyositis (JDM) is a rare, severe autoimmune disease and the most common idiopathic inflammatory myopathy of children. JDM and adult-onset dermatomyositis (DM) have similar clinical, biological and serological features, although these features differ in prevalence between childhood-onset and adult-onset disease, suggesting that age of disease onset may influence pathogenesis. Therefore, a JDM-focused genetic analysis was performed using the largest collection of JDM samples to date.

Metabolomics analysis identifies a lipidomic profile in treatment-naïve juvenile dermatomyositis patients vs healthy control subjects.

Objectives: To perform an exploratory study to identify a JDM serum metabolic profile that differs from healthy controls (HCs) and responds to immunosuppressive treatment.

Methods: Blood was collected from 9 HCs and 10 patients diagnosed with probable (n = 4) or definite (n = 6) JDM based on the criteria of Bohan and Peter for myositis, with 7 of the 10 providing longitudinal samples following initiation of treatment; these patients comprised the treatment-naïve cohort. Sera underwent mass spectroscopy-based measurements of targeted metabolic intermediates, including 15 amino acids, 45 acylcarnitines (ACs), 15 ceramides and 29 sphingomyelins.

Pilot Study of the Juvenile Dermatomyositis Consensus Treatment Plans: A CARRA Registry Study.

Objectives: To determine the feasibility of comparing the Childhood Arthritis and Rheumatology ResearchAlliance (CARRA) consensus treatment plans (CTP) in treating moderate new-onset juvenile dermatomyositis (JDM) using the CARRA registry, and to establish appropriate analytic methods to control for confounding by indication and missing data.

Methods: A pilot cohort of 39 patients with JDM from the CARRA registry was studied. Patients were assigned by the treating physician, considering patient/family preferences, to 1 of 3 CTP: methotrexate (MTX) and prednisone (MP); intravenous (IV) methylprednisolone, MTX, and prednisone (MMP); or IV methylprednisolone, MTX, prednisone, and IV immunoglobulin (MMPI).

A Clinically and Biologically Based Subclassification of the Idiopathic Inflammatory Myopathies Using Machine Learning.

Objective: Published predictive models of disease outcomes in idiopathic inflammatory myopathies (IIMs) are sparse and of limited accuracy due to disease heterogeneity. Computational methods may address this heterogeneity by partitioning patients based on clinical and biological phenotype.

Methods: To identify new patient groups, we applied similarity network fusion (SNF) to clinical and biological data from 168 patients with myositis (64 adult polymyositis [PM], 65 adult dermatomyositis [DM], and 39 juvenile DM [JDM]) in the Rituximab in Myositis trial.

Interferon Chemokine Score and Other Cytokine Measures Track With Changes in Disease Activity in Patients With Juvenile and Adult Dermatomyositis.

Objective: Our aim was to identify cytokines and chemokines in patients with adult dermatomyositis (DM) and juvenile dermatomyositis (JDM) that predict changes in disease activity.

Methods: Multiplexed immunoassays (Meso Scale Discovery) enabled simultaneous measurement of interferon (IFN)-regulated chemokines and other pro- and anti-inflammatory cytokines specific to differentiation of specific T-cell and innate pathways. Cytokine scores were computed for IFNCK (IP-10, MCP-1), Th1 (IFNɣ, TNFα, and IL2), Th2 (IL4, IL10, IL12, and IL 13), Th17 (IL6, IL17, IL1β), macrophage (MIP-1α, MIP-1β, IL8), and regulatory (IL10, TNFα) factors.

Juvenile dermatomyositis: advances in clinical presentation, myositis-specific antibodies and treatment.

Background: Juvenile dermatomyositis (JDM) is a chronic autoimmune disease characteristic by inflammation of small vessels within the skin, muscle and vital organs. But the clinical features and treatment of JDM have not been fully clarified.

Data Sources: Databases underwent through PubMed for articles about the clinical features, myositis-specific antibodies of JDM and its treatment, and we selected publications written in English which were relevant to the topic of this review.

Cultivating Research Skills During Clinical Training to Promote Pediatric-Scientist Development.

Physician-scientists represent a critical component of the biomedical and health research workforce. However, the proportion of physicians who spend a significant amount of effort on scientific research has declined over the past 40 years. This trend has been particularly noticeable in pediatrics despite recent scientific work revealing that early life influences, exposures, and health status play a significant role in lifelong health and disease.

Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups.

Objectives: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies.

A Path to Prediction of Outcomes in Juvenile Idiopathic Inflammatory Myopathy.

Humans have an innate desire to observe and subsequently dissect an event into component pieces in an effort to better characterize the event. We then examine these pieces individually and in combinations using this information to determine the outcome of future similar events and the likelihood of their recurrence. Practically, this attempt to foretell an occurrence and predict its outcomes is evident in multiple disciplines ranging from meteorology to sociologic studies.

T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients.

Background: Polymyositis (PM) and dermatomyositis (DM) are two distinct subgroups of idiopathic inflammatory myopathies, a chronic inflammatory disorder clinically characterized by muscle weakness and inflammatory cell infiltrates in muscle tissue. In PM, a major component of inflammatory cell infiltrates is CD8+ T cells, whereas in DM, CD4+ T cells, plasmacytoid dendritic cells, and B cells predominate. In this study, with the aim to differentiate involvement of CD4+ and CD8+ T-cell subpopulations in myositis subgroups, we investigated transcriptomic profiles of T cells from peripheral blood of patients with myositis.

Update on outcome assessment in myositis.

The adult and juvenile myositis syndromes, commonly referred to collectively as idiopathic inflammatory myopathies (IIMs), are systemic autoimmune diseases with the hallmarks of muscle weakness and inflammation. Validated, well-standardized measures to assess disease activity, known as core set measures, were developed by international networks of myositis researchers for use in clinical trials. Composite response criteria using weighted changes in the core set measures of disease activity were developed and validated for adult and juvenile patients with dermatomyositis and adult patients with polymyositis, with different thresholds for minimal, moderate and major improvement in adults and juveniles.

Brief Report: The Genetic Profile of Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis.

Objective: Juvenile idiopathic arthritis (JIA) comprises 7 heterogeneous categories of chronic childhood arthritides. Approximately 5% of children with JIA have rheumatoid factor (RF)-positive arthritis, which phenotypically resembles adult rheumatoid arthritis (RA). Our objective was to compare and contrast the genetics of RF-positive polyarticular JIA with those of RA and selected other JIA categories, to more fully understand the pathophysiologic relationships of inflammatory arthropathies.

EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a methodology report.

Objective: To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups.

Methods: An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children).

Predictors of changes in disease activity among children with juvenile dermatomyositis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry.

Determinants of changes in disease activity among patients with juvenile dermatomyositis (JDM) are unknown. Our objective was to develop predictive models to predict changes in disease activity using the CARRA Legacy Registry. The CARRA Legacy Registry included 658 subjects with definite or probably JDM with 297 subjects with a one follow-up visit after baseline, and we studied the 65 subjects with active disease at baseline.

2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups.

Objective: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.

Methods: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide.

Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research.

Objectives: This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres.

Methods: A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process.