Identification of Unique microRNA Profiles in Different Types of Idiopathic Inflammatory Myopathy.

Dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) are four major types of idiopathic inflammatory myopathy (IIM). Muscle biopsies from each type of IIM have unique transcriptomic profiles. MicroRNAs (miRNAs) target messenger RNAs (mRNAs), thereby regulating their expression and modulating transcriptomic profiles.

The pattern of MHC class I expression in muscle biopsies from patients with myositis and other neuromuscular disorders.

Objective: Diagnostic muscle biopsies are routinely immunostained for major histocompatibility complex class I (MHC-I) protein. In this study we analysed the prevalence and patterns of MHC-I immunostaining in biopsies from patients with different types of myopathies and neurogenic disorders.

Methods: All 357 diagnostic muscle biopsies processed at the Johns Hopkins Neuromuscular Pathology Laboratory from August 2013 to January 2017 were immunostained for MHC-I.

Loss of TDP-43 function and rimmed vacuoles persist after T cell depletion in a xenograft model of sporadic inclusion body myositis.

Sporadic inclusion body myositis (IBM) is the most common acquired muscle disease in adults over age 50, yet it remains unclear whether the disease is primarily driven by T cell–mediated autoimmunity. IBM muscle biopsies display nuclear clearance and cytoplasmic aggregation of TDP-43 in muscle cells, a pathologic finding observed initially in neurodegenerative diseases, where nuclear loss of TDP-43 in neurons causes aberrant RNA splicing. Here, we show that loss of TDP-43–mediated splicing repression, as determined by inclusion of cryptic exons, occurs in skeletal muscle of subjects with IBM.

Accumulation of autophagosome cargo protein p62 is common in idiopathic inflammatory myopathies.

Objectives: The subsarcolemmal accumulation of p62 aggregates in myofibres has been proposed to be characteristic of sporadic inclusion body myositis (sIBM). The objective of this study was to analyse the patterns and prevalence of p62 immunostaining and to quantitate p62 gene expression in muscle biopsies from a large number of patients with different types of myopathic and neurogenic disorders.

Methods: For the p62 immunostaining analysis, all patients with a muscle biopsy immunostained for p62 at the Johns Hopkins Neuromuscular Pathology Laboratory from 2013 to 2017 were included (n=303).

Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis.

Objectives: Myositis is a heterogeneous family of diseases that includes dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM), inclusion body myositis (IBM), polymyositis and overlap myositis. Additional subtypes of myositis can be defined by the presence of myositis-specific autoantibodies (MSAs). The purpose of this study was to define unique gene expression profiles in muscle biopsies from patients with MSA-positive DM, AS and IMNM as well as IBM.

More prominent muscle involvement in patients with dermatomyositis with anti-Mi2 autoantibodies.

Objective: To define the clinical phenotype of dermatomyositis (DM) with anti-Mi2 autoantibodies.

Methods: In this longitudinal cohort study, the prevalence and severity of clinical features at disease onset and during follow-up in patients with anti-Mi2-positive DM were compared to patients with anti-Mi2-negative DM, antisynthetase syndrome (AS), and immune-mediated necrotizing myopathy (IMNM). Longitudinal anti-Mi2 autoantibody titers were assessed.

Stopping oral steroid-sparing agents at initiation of rituximab in myasthenia gravis.

Rituximab is a chimeric monoclonal antibody that binds CD20 and causes the depletion of B-cell subsets. Although initially designed to treat lymphoma, it has found wide use in the management of various autoimmune conditions, including myasthenia gravis (MG), an autoimmune disorder of the neuromuscular junction. Treated myasthenia patients are often on an oral steroid-sparing agent.

Myositis Autoantigen Expression Correlates With Muscle Regeneration but Not Autoantibody Specificity.

Objective: Although more than a dozen myositis-specific autoantibodies (MSAs) have been identified, most patients with myositis are positive for a single MSA. The specific overexpression of a given myositis autoantigen in myositis muscle has been proposed as initiating and/or propagating autoimmunity against that particular autoantigen. The present study was undertaken to test this hypothesis.

Muscular and extramuscular features of myositis patients with anti-U1-RNP autoantibodies.

Objective: To define the clinical phenotype of patients with myositis with anti-U1-ribonucleoprotein (RNP) autoantibodies.

Methods: In this longitudinal cohort study, the prevalence and severity of clinical features at disease onset and during follow-up in patients with anti-U1-RNP-positive myositis were compared to those with dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), and the antisynthetase syndrome (AS).

Results: Twenty anti-U1-RNP-positive patients, 178 patients with DM, 135 patients with IMNM, and 132 patients with AS were included.

Muscular and extramuscular clinical features of patients with anti-PM/Scl autoantibodies.

Objective: To define the clinical features of myositis patients with anti-PM/Scl-75 and/or anti-PM/Scl-100 autoantibodies at disease onset and during the course of disease and compare them to patients with other forms of myositis.

Methods: In this longitudinal cohort study, the prevalence and severity of clinical features at disease onset and during follow-up were compared between anti-PM/Scl-positive patients and those with the antisynthetase syndrome (AS), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM).

Results: Forty-one anti-PM/Scl-positive, 132 AS, 178 DM, and 135 IMNM patients were included.

Inflammatory myopathy associated with anti-mitochondrial antibodies: A distinct phenotype with cardiac involvement.

Objective: In the context of clinical evaluations performed on our prospective myositis cohort, we noted a striking association of severe cardiac disease in myositis patients with anti-mitochondrial antibodies. We sought to review all cases of anti-mitochondrial antibody (AMA) associated myositis in our cohort to describe the clinical features of this disease subset.

Methods: We identified 7 patients with confirmed anti-mitochondrial antibodies who presented as an inflammatory myopathy.

Association of Fibrosing Myopathy in Systemic Sclerosis and Higher Mortality.

Objective: To determine if a unique subtype of scleroderma muscle disease exists by comparing the clinical features of systemic sclerosis (SSc; scleroderma) patients with predominant fibrosis on muscle biopsy to those with inflammatory muscle histopathology.

Methods: This retrospective, cross-sectional study included SSc patients with muscle weakness and an available muscle biopsy. Biopsies with fibrosis but without inflammation/necrosis were designated as "fibrosing myopathy," and those with inflammation and/or necrosis were assigned a category of "inflammatory myopathy.

Calcium dysregulation, functional calpainopathy, and endoplasmic reticulum stress in sporadic inclusion body myositis.

Sporadic inclusion body myositis (IBM) is the most common primary myopathy in the elderly, but its pathoetiology is still unclear. Perturbed myocellular calcium (Ca) homeostasis can exacerbate many of the factors proposed to mediate muscle degeneration in IBM, such as mitochondrial dysfunction, protein aggregation, and endoplasmic reticulum stress. Ca dysregulation may plausibly be initiated in IBM by immune-mediated membrane damage and/or abnormally accumulating proteins, but no studies to date have investigated Ca regulation in IBM patients.

Hemiparetic Primary Lateral Sclerosis: Revisiting Mills Syndrome.

A slowly progressive hemiparesis beginning in a single limb with evolution to the ipsilateral limb was originally described in 8 patients in 1906 by Mills. We present 5 cases of progressive hemiparetic corticospinal tract degeneration, identified by the clinical presentation and the exclusion of other etiologies using serological, imaging, and electrodiagnostic studies.

The Prevalence of Individual Histopathologic Features Varies according to Autoantibody Status in Muscle Biopsies from Patients with Dermatomyositis.

Objective: Individual dermatomyositis (DM)-associated autoantibodies are associated with distinct clinical phenotypes. This study was undertaken to explore the association of these autoantibodies with specific muscle biopsy features.

Methods: DM subjects with a muscle biopsy reviewed at Johns Hopkins had sera screened for autoantibodies recognizing Mi-2, transcriptional intermediary factor 1-γ (TIF1-γ), NXP2, MDA5, Ro52, PM-Scl, and Jo1.

Sulfatide levels correlate with severity of neuropathy in metachromatic leukodystrophy.

Objective: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder due to deficient activity of arylsulfatase A (ASA) that causes accumulation of sulfatide and lysosulfatide. The disorder is associated with demyelination and axonal loss in the central and peripheral nervous systems. The late infantile form has an early-onset, rapidly progressive course with severe sensorimotor dysfunction.

Spectrum of Muscle Histopathologic Findings in Forty-Two Scleroderma Patients With Weakness.

Objective: To determine if distinct muscle pathologic features exist in scleroderma subjects with weakness.

Methods: This retrospective study included weak scleroderma subjects with muscle biopsies available for review. Biopsies were systematically assessed for individual pathologic features, including inflammation, necrosis, fibrosis, and acute neurogenic atrophy.

Laing distal myopathy pathologically resembling inclusion body myositis.

Mutations in MYH7 cause autosomal dominant Laing distal myopathy. We present a family with a previously reported deletion (c.5186_5188delAGA, p.

The co-existence of myasthenia gravis in patients with myositis: a case series.

Objective: Myositis and myasthenia gravis (MG) are both autoimmune disorders presenting with muscle weakness. Rarely, they occur simultaneously in the same patient. Since the management of myasthenia gravis differs from that of myositis, it is important to recognize when patients have both diseases.

Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease.

Objectives: To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity.

Methods: 55 patients with JDM with muscle biopsy tissue and clinical data available were included.

Expanding the spectrum of monoclonal light chain deposition disease in muscle.

Introduction: The diagnosis of amyloid myopathy is delayed when monoclonal gammopathies are not detected on initial testing and muscle biopsies are nondiagnostic, and the EMG and symptoms can mimic an inflammatory myopathy.

Methods: Case report of a patient presenting with severe progressive muscle weakness of unclear etiology despite an extensive workup including two nondiagnostic muscle biopsies.

Results: Directed by MRI, a third biopsy revealed amyloid angiopathy and noncongophilic kappa light chain deposition in scattered subsarcolemmal rings and perimysial regions.

Recombinant expression of the AChR-alpha1 subunit for the detection of conformation-dependent epitopes in Myasthenia Gravis.

Detection of autoantibodies associated with neurological disease typically involves immunoprecipitation of radioactively labeled native proteins. We explored whether single receptor subunits, fused to Renilla luciferase (Ruc), could detect patient autoantibodies in Luciferase Immunoprecipitation Systems. Myasthenia Gravis patient sera were tested for conformational autoantibodies to only the α1-subunit of the nicotinic acetylcholine receptor (AChR).

A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy.

Objective: Myofiber necrosis without prominent inflammation is a nonspecific finding in patients with dystrophies and toxic or immune-mediated myopathies. However, the etiology of a necrotizing myopathy is often obscure, and the question of which patients would benefit from immunosuppression remains unanswered. The aim of this study was to identify novel autoantibodies in patients with necrotizing myopathy.