A5088098447- Inflammatory Myopathies and Dermatomyositis
- Muscle Physiology and Disorders
- Eosinophilic Disorders and Syndromes
- Immunodeficiency and Autoimmune Disorders
- T-cell and B-cell Immunology
- Neurogenetic and Muscular Disorders Research
- Systemic Sclerosis and Related Diseases
- Intracerebral and Subarachnoid Hemorrhage Research
- Genetic Neurodegenerative Diseases
- Skin Diseases and Diabetes
- Celiac Disease Research and Management
- Peripheral Neuropathies and Disorders
- Muscle and Compartmental Disorders
- Heterotopic Ossification and Related Conditions
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Parkinson's Disease and Spinal Disorders
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Cutaneous lymphoproliferative disorders research
- T-cell and Retrovirus Studies
- Chronic Lymphocytic Leukemia Research
- Galectins and Cancer Biology
- Dermatological and Skeletal Disorders
- Hereditary Neurological Disorders
Brigham and Women's Hospital
2016-2025
Harvard University
2016-2025
Massachusetts General Hospital
2002-2025
MaineHealth
2024-2025
Boston Children's Hospital
2012-2024
Duke University
2023
University of Alabama at Birmingham
2023
University of Pennsylvania
2023
Johns Hopkins University
2014-2022
University of California, Irvine
2022
Accurate and rapid identification of perturbed pathways through the analysis genome-wide expression profiles facilitates generation biological hypotheses. We propose a statistical framework for determining whether specified group genes pathway has coordinated association with phenotype interest. Several issues on proper hypothesis-testing procedures are clarified. In particular, it is shown that differences in correlation structure each set can lead to biased comparison among gene sets...
Abstract Dermatomyositis has been modeled as an autoimmune disease largely mediated by the adaptive immune system, including a local humorally response with B and T helper cell muscle infiltration, antibody complement‐mediated injury of capillaries, perifascicular atrophy fibers caused ischemia. To further understand pathophysiology dermatomyositis, we used microarrays, computational methods, immunohistochemistry electron microscopy to study specimens from 67 patients, 54 inflammatory...
<b>Objective</b> To understand belief in a specific scientific claim by studying the pattern of citations among papers stating it. <b>Design</b> A complete citation network was constructed from all PubMed indexed English literature addressing that β amyloid, protein accumulated brain Alzheimer's disease, is produced and injures skeletal muscle patients with inclusion body myositis. Social theory graph were used to analyse this network. <b>Main outcome measures</b> Citation bias,...
<h3>Objective</h3> To characterise activation of the type I interferon (IFN) pathway in patients with systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), rheumatoid arthritis (RA) and scleroderma (SSc) to evaluate potential develop a molecular diagnostic tool from peripheral blood that reflects this disease-affected tissues. <h3>Methods</h3> Overexpressed transcripts were identified whole (WB) 262 SLE, 44 DM, 33 PM, 28 SSc 89 RA compared 24 healthy subjects using...
Abstract We report patients from two neuromuscular centers who were evaluated between the years 2000 and 2008 met following criteria: (1) proximal muscle weakness occurring during or after treatment with statins; (2) elevated serum creatine kinase (CK); (3) persistence of CK despite discontinuation statin; (4) improvement immunosuppressive agents; (5) biopsy showing necrotizing myopathy without significant inflammation. Twenty‐five fulfilled our inclusion criteria. Twenty‐four required...
Objective We previously identified a circulating autoantibody against 43 kDa muscle autoantigen in sporadic inclusion body myositis (IBM) and demonstrated the feasibility of an IBM diagnostic blood test. Here, we sought to identify molecular target this autoantibody, understand relationship between autoimmunity degeneration, develop test with high accuracy. Methods samples were screened using mass spectrometry synthetic human peptidome. Plasma serum (N=200 patients) underwent immunoblotting...
<h3>Objective:</h3> To study activin signaling and its blockade in sporadic inclusion body myositis (sIBM) through translational studies a randomized controlled trial. <h3>Methods:</h3> We measured transforming growth factor β by SMAD2/3 phosphorylation muscle biopsies of 50 patients with neuromuscular disease (17 sIBM). tested inhibition receptors IIA IIB (ActRII) 14 sIBM using one dose bimagrumab (n = 11) or placebo 3). The primary outcome was the change right thigh volume MRI at 8 weeks....
The primary cause of Duchenne muscular dystrophy (DMD) is a mutation in the dystrophin gene leading to absence corresponding RNA transcript and protein. Absence leads disruption dystrophin-associated protein complex substantial changes skeletal muscle pathology. Although histological pathology dystrophic tissue has been well documented, underlying molecular pathways remain poorly understood. To examine pathogenic identify new or modifying factors involved dystrophy, expression microarrays...
Abstract Objective To apply gene expression profiling to the study of peripheral blood mononuclear cells from patients with inflammatory myopathies, in order provide insight into disease pathogenesis and identify potential biomarkers associated activity. Methods We used Affymetrix whole‐genome microarrays measure ∼38,500 genes 65 15 muscle samples 44 dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), myasthenia gravis, or genetically determined myopathies 12 healthy...
<b><i>Objective: </i></b> To describe the use of large-scale gene expression profiles to distinguish broad categories myopathy and subtypes inflammatory myopathies (IM) provide insight into pathogenesis inclusion body myositis (IBM), polymyositis, dermatomyositis. <b><i>Methods: Using Affymetrix GeneChip microarrays, authors measured simultaneous approximately 10,000 genes in muscle specimens from 45 patients four major disease (dystrophy, congenital myopathy, normal). The separately...
Abstract The nucleic acid binding protein TDP‐43 was recently identified in normal myonuclei and the sarcoplasm of inclusion body myositis (IBM) muscle. Here we found sarcoplasmic immunoreactivity 23% IBM myofibers, while other reported biomarkers were less frequent, with rimmed vacuoles 2.8%, fluorescent Congo red material 0.57%, SMI‐31 0.83%, focal R1282 beta‐amyloid 0.00% myofibers. presence as little >1% myofibers nonnuclear highly sensitive (91%) specific (100%) to among 50...
Background: Previous immunohistochemical studies of muscle from patients with inclusion body myositis and polymyositis found many more T cells than B cells, suggesting a role for intramuscular cell-mediated immune mechanisms rather humoral mechanisms.
Abstract Objective We investigated interferon‐stimulated gene 15 (ISG15), a poorly understood ubiquitin‐like modifier, and its enzymatic pathway in dermatomyositis (DM), an autoimmune disease primarily involving muscle skin. Methods generated microarray data measuring transcript abundance for approximately 18,000 genes each of 113 human biopsy specimens, studied specimens cultured skeletal using immunohistochemistry, immunoblotting proteomics, real‐time quantitative polymerase chain...
<h3>Objective</h3> To assess the pharmacodynamic effects of sifalimumab, an investigational anti-IFN-α monoclonal antibody, in blood and muscle adult dermatomyositis polymyositis patients by measuring neutralisation a type I IFN gene signature (IFNGS) following drug exposure. <h3>Methods</h3> A phase 1b randomised, double-blinded, placebo controlled, dose-escalation, multicentre clinical trial was conducted to evaluate sifalimumab or patients. Blood biopsies were procured before after...
The objective of this study was to evaluate the relationship between blood mRNA, disease activity and treatment effects in a longitudinal patients with dermatomyositis (DM) or polymyositis (PM). In all, 24 DM PM were followed for up 6 years (mean 1.9 years) at 2-7 follow-up visits while receiving standard clinical care. Clinical data samples collected 80 patient used analysis cytokine-induced gene expression signaling pathways type 1 interferon (IFN), tumor necrosis factor-α, IL-1β,...
Objective The molecular basis of inflammatory myopathies such as dermatomyositis (DM), polymyositis, and inclusion body myositis, which share the characteristics chronic muscle inflammation skeletal wasting, are poorly understood. As such, effective targeted treatments for these diseases lacking, resulting in critical unmet medical needs devastating diseases. purpose this study was to identify possible new targets drug development by exploring mechanism may play a role pathology myopathies....
Inclusion body myositis (IBM) is a poorly understood and refractory autoimmune muscle disease. Though widely believed to have no significant humoral autoimmunity, we sought identify novel autoantibodies with high specificity for this disease.Plasma from 65 people, including 25 IBM, were analyzed by immunoblots against normal human muscle. Thirteen of (52%) IBM patient samples recognized an approximately 43 kDa protein. No other disease (N = 25) or healthy volunteer 15) protein.Circulating...
Dermatomyositis (DM) is an autoimmune disease primarily affecting skin and muscle. The purpose of this study was to determine whether association exists between clinical activity as measured by the validated Cutaneous Disease Area Severity Index (CDASI) type 1 interferon (IFN) pathway biomarkers in blood patients with DM. Forty‐two DM 25 healthy volunteers were prospectively enrolled. CDASI scores obtained, serum RNA isolated from all participants. Associations IFN‐inducible gene signature...
See Hohlfeld and Schulze-Koops (doi: 10.1093/brain/aww053 ) for a scientific commentary on this article. Inclusion body myositis T cell large granular lymphocytic leukaemia are rare diseases involving pathogenic cytotoxic CD8+ cells. After encountering four patients with both disorders, we prospectively screened 38 inclusion the presence of expanded lymphocyte populations by standard clinical laboratory methods (flow cytometry, examination blood smears, receptor gene rearrangements),...
Inclusion body myositis is a late onset treatment-refractory autoimmune disease of skeletal muscle associated with blood autoantibody (anti-cN1A), an HLA haplotype, and pathology characterized by cytotoxic CD8+ T cell destruction myofibres. Here, we report on translational studies inclusion patient compared diverse set other samples. Using available microarray data 411 samples from patients (n = 40), diseases 265), without neuromuscular (normal, n 106), identified signature T-cell...
Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, pathologic significance these autoantibodies has been questioned due to assumption that cannot enter living muscle cells. This study aims investigate validity this assumption.