Myositis-Associated Autoantibodies in Patients With Juvenile Myositis Are Associated With Refractory Disease and Mortality.

Objective: Myositis-associated autoantibodies (MAAs) have been associated with overlap myositis, certain disease manifestations such as interstitial lung disease (ILD), and worse prognosis in the idiopathic inflammatory myopathies. MAAs overall remain largely uncharacterized in patients with juvenile-onset myositis. Moreover, it is unknown whether the number of MAAs is associated with disease severity.

Autoantibodies Recognizing Specificity Protein 4 Co-occur With Anti-Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis.

Objective: Autoantibodies recognizing specificity protein 4 (Sp4) were recently discovered in adults with idiopathic inflammatory myopathies (IIM). Anti-Sp4 autoantibodies co-occurred in patients with anti-transcription intermediary factor 1 (anti-TIF1) autoantibody-positive dermatomyositis (DM) and were associated with a reduced risk of cancer. In the present study, the prevalence and clinical features associated with anti-Sp4 autoantibodies in juvenile-onset IIM were investigated.

Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features.

Objectives: Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children.

Environmental factors associated with juvenile idiopathic inflammatory myopathy clinical and serologic phenotypes.

Background: Environmental exposures have been associated with the juvenile idiopathic inflammatory myopathies (JIIM). We undertook a questionnaire-based study to evaluate patient-reported exposures as possible risk factors for JIIM.

Findings: One-hundred-seven patients with JIIM were enrolled in a myositis natural history protocol and completed environmental questionnaires.

Association of anti-HSC70 autoantibodies with cutaneous ulceration and severe disease in juvenile dermatomyositis.

Objectives: JDM is an inflammatory myopathy characterized by prominent vasculopathy. AECAs are frequently detected in inflammatory and autoimmune diseases. We sought to determine whether AECAs correlate with clinical features of JDM, and thus serve as biomarkers to guide therapy or predict outcome.

Anti-MDA5 autoantibodies associated with juvenile dermatomyositis constitute a distinct phenotype in North America.

Objective: Myositis-specific autoantibodies have defined distinct phenotypes of patients with juvenile myositis (JIIM). We assessed the frequency and clinical significance of anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody-associated JIIM in a North American registry.

Methods: Retrospective examination of the characteristics of 35 JIIM patients with anti-MDA5 autoantibodies was performed, and differences from other myositis-specific autoantibody groups were evaluated.

Corticosteroid discontinuation, complete clinical response and remission in juvenile dermatomyositis.

Objective: A North American registry of JDM patients was examined for frequency of and factors associated with corticosteroid discontinuation, complete clinical response and remission.

Methods: We evaluated probability of achieving final corticosteroid discontinuation, complete clinical response and remission in 307 JDM patients by Weibull time-to-event modelling; conditional probability of complete clinical response and remission using Bayesian network modelling; and significant predictors with multivariable Markov chain Monte-Carlo Weibull extension models.

Results: The probability of corticosteroid discontinuation was 56%, complete clinical response 38% and remission 30% by 60 months after initial treatment in 105 patients.

Recognising the spectrum of scleromyositis: HEp-2 ANA patterns allow identification of a novel clinical subset with anti-SMN autoantibodies.

Objective: To describe systemic sclerosis (SSc) with myopathy in patients without classic SSc-specific and SSc-overlap autoantibodies (aAbs), referred to as seronegative scleromyositis.

Methods: Twenty patients with seronegative scleromyositis diagnosed by expert opinion were analysed retrospectively for SSc features at myositis diagnosis and follow-up, and stratified based on HEp-2 nuclear patterns by indirect immunofluorescence (IIF) according to International Consensus of Autoantibody Patterns. Specificities were analysed by protein A-assisted immunoprecipitation.

Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies.

Background: Juvenile dermatomyositis (JDM) is a systemic autoimmune disease with a prominent interferon (IFN) signature, but the pathogenesis of JDM and the etiology of its IFN signature remain unknown. The Mendelian autoinflammatory interferonopathies, Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) and STING-Associated Vasculopathy with onset in Infancy (SAVI), are caused by genetic mutations and have extremely elevated IFN signatures thought to drive pathology. The phenotypic overlap of some clinical features of CANDLE and SAVI with JDM led to the comparison of a standardized interferon-regulated gene score (IRG-S) in JDM and myositis-specific autoantibody (MSA) JDM subgroups, with CANDLE and SAVI.

Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients.

Objective: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy.

Methods: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies.

Results: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%).

Anti-Ro52 autoantibodies are associated with interstitial lung disease and more severe disease in patients with juvenile myositis.

Objectives: Anti-Ro52 autoantibodies are associated with more severe interstitial lung disease (ILD) in adult myositis patients with antiaminoacyl transfer (t)RNA synthetase autoantibodies. However, few studies have examined anti-Ro52 autoantibodies in juvenile myositis. The purpose of this study was to define the prevalence and clinical features associated with anti-Ro52 autoantibodies in a large cohort of patients with juvenile myositis.

SDS-PAGE for S Immunoprecipitation and Immunoprecipitation Western Blotting.

This report discusses recent methods of sample preparation and gel electrophoresis for S immunoprecipitation (IP) and IP western blotting. In both methods, IP is used to obtain purified proteins, and sodium dodecyl sulfate polyacrylamide gel electrophoresis is used to separate the proteins on a gel. In S IP, the proteins are radiolabeled and visualized on film by fluorography; in IP blotting, proteins are transferred onto nitrocellulose paper, and antibodies are used to detect specific proteins.

Medications received by patients with juvenile dermatomyositis.

Objective: Few controlled studies are available to guide treatment decisions in juvenile dermatomyositis (JDM). This study evaluated therapies received, changes of treatment over time, and factors associated with medication choices in JDM.

Methods: We performed a retrospective analysis of the number and type of therapies and duration of treatment for 320 patients with JDM enrolled in a North American registry.

The effect of cigarette smoking on the clinical and serological phenotypes of polymyositis and dermatomyositis.

Objective: Cigarette smoking is associated with immune-mediated disorders. We explored the contribution of smoking to polymyositis (PM) and dermatomyositis (DM) phenotypes and attempted to determine whether cigarette smoking effects differ by race and genotype.

Methods: Associations of tobacco smoking with disease features, autoantibodies, HLA types, and race were evaluated using multiple logistic regressions in 465 patients.

Anti-NT5C1A autoantibodies are associated with more severe disease in patients with juvenile myositis.

Objectives: Autoantibodies recognising cytosolic 5'-nucleotidase 1A (NT5C1A) are found in adult patients with myositis and other autoimmune diseases. They are especially prevalent in adults with inclusion body myositis (IBM), in which they are associated with more severe weakness and higher mortality. This study was undertaken to define the prevalence and clinical features associated with anti-NT5C1A autoantibodies in juvenile myositis.

Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients.

Objective: Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are associated with statin exposure, the HLA allele DRB1*11:01, and necrotizing muscle biopsies in adult myositis patients. The aim of this study was to characterize the features of juvenile anti-HMGCR-positive myositis patients.

Methods: The sera of 440 juvenile myositis patients were screened for anti-HMGCR autoantibodies.

Monitoring change in volume of calcifications in juvenile idiopathic inflammatory myopathy: a pilot study using low dose computed tomography.

Background: Dystrophic calcifications may occur in patients with J uvenile Idiopathic Inflammatory Myopathy (JIIM) as well as other connective tissue and metabolic diseases, but a reliable method of measuring the volume of these calcifications has not been established. The purpose of this study is to determine the feasibility of low dose, limited slice, Computed Tomography (CT) to measure objectively in-situ calcification volumes in patients with JIIM over time.

Methods: Ten JIIM patients (eight JDM, two Overlap) with calcifications were prospectively recruited over a 2-year period to undergo two limited, low dose, four-slice CT scans.

Brief Report: Association of Myositis Autoantibodies, Clinical Features, and Environmental Exposures at Illness Onset With Disease Course in Juvenile Myositis.

Objective: To identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (IIMs).

Methods: Univariable and multivariable multinomial logistic regression analyses were performed in a large juvenile IIM registry (n = 365) and included demographic characteristics, early clinical features, serum muscle enzyme levels, myositis autoantibodies, environmental exposures, and immunogenetic polymorphisms.

Results: Multivariable associations with chronic or polycyclic courses compared to a monocyclic course included myositis-specific autoantibodies (multinomial odds ratio [OR] 4.

Immunoprecipitation: Western blot for proteins of low abundance.

Combining the procedures of immunoprecipitation and immunoblotting can help overcome some of the limitations of each separate procedure. Immunoblotting can identify immunoprecipitated proteins more specifically and with higher sensitivity than nonspecific protein stains or autoradiography. Immunoprecipitation can enrich proteins of interest to improve sensitivity for detection when compared with immunoblotting of whole cell extracts.

An autoimmune myositis-overlap syndrome associated with autoantibodies to nuclear pore complexes: description and long-term follow-up of the anti-Nup syndrome.

Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss.

Redefining dermatomyositis: a description of new diagnostic criteria that differentiate pure dermatomyositis from overlap myositis with dermatomyositis features.

Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM.