Development and validation of a Bayesian survival model for inclusion body myositis
Associations between disease characteristics and payer-relevant outcomes can be difficult to establish for rare and progressive chronic diseases with sparse available data. We developed an exploratory bridging... (Source: Theoretical Biology and Medical Modelling)
Source: Theoretical Biology and Medical Modelling - November 7, 2019 Category: Biomedical Science Authors: Gorana Capkun, Jens Schmidt, Shubhro Ghosh, Harsh Sharma, Thomas Obadia, Ana de Vera, Valery Risson and Billy Amzal Tags: Research Source Type: research

Texture analysis of sonographic muscle images can distinguish myopathic conditions.
Authors: Nodera H, Sogawa K, Takamatsu N, Hashiguchi S, Saito M, Mori A, Osaki Y, Izumi Y, Kaji R Abstract Given the recent technological advent of muscle ultrasound (US), classification of various myopathic conditions could be possible, especially by mathematical analysis of muscular fine structure called texture analysis. We prospectively enrolled patients with three neuromuscular conditions and their lower leg US images were quantitatively analyzed by texture analysis and machine learning methodology in the following subjects :  Inclusion body myositis (IBM) [N=11] ; myotonic dystrophy type 1 (DM1) [N=19...
Source: Journal of Medical Investigation - October 29, 2019 Category: General Medicine Tags: J Med Invest Source Type: research

Insights into Design of p97-targeting Small Molecules from Structural Studies on p97 Functional Mechanism.
Abstract p97, also known as valosin-containing protein or CDC48, is a member of the AAA+ protein family that is highly conserved in eukaryotes. It binds to various cofactors in the body to perform its protein-unfolding function and participates in DNA repair, degradation of subcellular membrane proteins, and protein quality control pathways, among other processes. Its malfunction can lead to many diseases, such as inclusion body myopathy, associated with Paget's disease of bone and/or frontotemporal dementia, amyotrophic lateral sclerosis disease, and others. In recent years, many small molecule inhibitors have be...
Source: Current Medicinal Chemistry - October 4, 2019 Category: Chemistry Authors: Sui X, Pan M, Li YM Tags: Curr Med Chem Source Type: research

P.304Ultrafast simultaneous characterization of muscle inflammation and fatty replacement in inclusion body myositis with magnetic resonance fingerprinting (MRF)
Quantitative NMR T1 mapping might be an appealing alternative for monitoring disease activity in neuromuscular disorders (NMDs), knowing it has been validated to monitor inflammation, necrosis or fibrosis in cardiac muscle. However, T1 values are confounded by the presence of fat in diseased muscles. Recently, we proposed a magnetic resonance fingerprinting (MRF) method that separates water and fat (MRF-WF), allowing simultaneous estimation of water T1 (T1H2O) and fat fraction (FF). Here, we investigated the potential of T1H2O for monitoring disease activity in inclusion body myositis (IBM) patients. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: B. Marty, H. Reyngoudt, P. Carlier Source Type: research

Mri – muscle imaging
The degree of fatty infiltration, as measured using water-fat NMR imaging separation techniques (such as Dixon) is now a widely accepted muscle imaging biomarker and an often proposed outcome measure in many neuromuscular disease longitudinal studies. The question remains which is the specific muscle (group) to evaluate during the study period. We aimed to compare different segmentation approaches (global vs individual muscles) in a variety of neuromuscular disorders: immune-mediated necrotizing myopathy (IMNM), inclusion body myositis (IBM), GNE myopathy (GNEM), Duchenne muscular dystrophy (DMD), limb-girdle muscular dyst...
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: H. Reyngoudt, J. Boisserie, J. Le Lou ër, C. Koumako, P. Baudin, B. Wong, T. Stojkovic, A. Behin, T. Gidaro, L. Servais, Y. Allenbach, O. Benveniste, B. Marty, P. Carlier Source Type: research

O.31Proteomic profiling unravels a key role of CD74, CD163 and STAT1 in sporadic inclusion body myositis
Inclusion body myositis is a chronic muscle-specific disease of adulthood leading to progressive paresis and swallowing difficulties. Muscle biopsy reveals a severe myopathic/dystrophic process with a complex inflammatory infiltrate and presence of protein deposits. Despite the characteristic clinical picture and well-known biopsy findings, the pathogenesis of sIBM is still elusive and not fully understood. In the current study, we applied unbiased proteomic profiling and identified the chaperone and cell surface marker CD74, the macrophage scavenger molecule CD163 and the transcription activator STAT1 to be among the high...
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: C. Preusse, A. Roos, D. Hathazi, H. Goebel, W. Stenzel Source Type: research

Diagnostic and experimental treatment approaches
Molecular pathogenesis of sporadic inclusion body myositis (sIBM) is complicated and poorly understood. It is, however, necessary to understand in order to implement a suitable therapeutic option. Due to the coexistence of inflammatory and muscle degenerative features, it is challenging to ascertain the underlying cause of muscle degeneration. Using an unbiased approach, we performed whole transcriptome analysis on microdissected biopsies of 41 human skeletal muscle samples, which include clinically and histopathologically defined sIBM, a myopathy control with clear genetic and histopathologic evidence and a non-muscle phe...
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: M. Johari, M. Savarese, A. Vihola, J. Palmio, M. Jokela, J. Buzkova, L. Pihlajamaki, A. Wartiovaara, P. Hackman, B. Udd Source Type: research

EP.13Long-lasting corticosteroids-induced improvement in inclusion body myositis with prominent mitochondrial changes
We describe a 62-year-old man, developing dysphagia over ten years and four limbs weakness over six months. Clinical examination showed mainly forearm flexor, psoas, quadriceps and feet extensor asymmetric weakness. There was mild elevated creatine kinase (50%). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: C. Damien, N. Mavroudakis, H. Kadhim, G. Remiche Source Type: research

P.21Genetic analysis of first-degree relatives with inclusion body myositis
Inclusion body myositis (IBM) is a sporadic clinicopathologically defined myopathy characterised by finger flexor and quadriceps weakness, along with the histological triad of endomysial autoaggressive inflammation, rimmed vacuoles and protein aggregates. Rare familial occurrences of IBM have however been reported. We have identified 3 such families. Families 1 and 2 consisted of pairs of affected siblings, while family 3 consisted of a mother and her two children. The onset of symptoms was between 55 and 73 years. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: S. Nicolau, Z. Niu, K. Ling, M. Milone Source Type: research

P.17Xenograft model of sporadic inclusion body myositis
Fundamental obstacles to the development of therapies for sporadic inclusion body myositis (IBM) include our limited understanding of disease pathogenesis as well as a lack of animal models. The primary invasion of myofibers by CD8+ T cells, an increased association of IBM with specific HLA haplotypes and other autoimmune diseases, and the presence of autoantibodies in many patients suggests that IBM is primarily an autoimmune disease. However, an association with aging, a lack of response to immunotherapy, and presence of ubiquitinated protein aggregates suggest the immune response may be secondary to myodegeneration. (So...
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: K. Britson, K. Russell, W. Tsao, J. Montagne, B. Larman, K. Wagner, L. Ostrow, T. Lloyd Source Type: research

P.12Active immunization mouse model of sporadic inclusion body myositis by cN1A peptides
Sporadic inclusion body myositis (sIBM) is an intractable progressing inflammatory myopathy frequently affects elderly people. Lack of effective treatments and unclearness of pathogenesis in sIBM may be associated with absence of appropriate animal models. Recently, autoantibodies recognizing cytoplasmic 5 ′-nucleotidase 1a (cN1A) have been found in the sera of sIBM patients. However the roles of the anti-cN1A autoantibodies and autoreactive T cells are still unknown. In the current study, we aimed to generate the active immunization mouse model by cN1A peptides to realize the pathogenesis of sIBM. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: N. Tawara, Z. Zhang, S. Yamashita, K. Hara, X. Zhang, T. Doki, S. Nakane, Y. Ando Source Type: research

P.08Interferon level assessed by ultrasensitive detection technology in myositis patients: a promising biomarker of disease activity in dermatomyositis and anti-synthetase syndrome
Inflammatory idiopathic myopathies (IIM) are a heterogeneous group of disorders ranging from muscle specific auto-immune diseases to systemic ones (dermatomyositis (DM), anti-synthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM) and inclusion body myositis (IBM)). Recent insight into DM pathogenesis highlighted the role of type I interferon (IFN) and the level of IFN-pathway activity is linked to those of the disease. The aim of this study was to measure IFN- α, β and γ seric level in the different groups of myositis using an ultrasensitive detection technology to evaluate IFN-α as ...
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: L. Bolko, C. Anquetil, S. Maillard, O. Landon-Cardinal, S. Toquet, K. Dorgham, N. Wesner, D. Amelin, G. Dzangue-Tchoupou, A. Llibre-Seradel, D. Duffy, P. Guillaume-Jugnot, A. Rigolet, B. Hervier, M. Vautier, N. Champtiaux, G. Gorochov, O. Benveniste, Y. A Source Type: research

P.06Muscle ultrasound in patients with inclusion body myositis: differentiating from mimics
In this study we aimed to further evaluate the ability of US to differentiate between IBM and Polymyositis/Dermatomyositis (PM/DM) and neuromuscular disorders using two separate cohorts. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: K. Leeuwenberg, L. Christopher-Stine, J. Paik, E. Tiniakou, C. Mecoli, N. van Alfen, J. Doorduin, C. Saris, J. Albayda Source Type: research

P.05Feasibility and validation of modified oculobulbar facial respiratory score (mOBFRS) in sporadic inclusion body myositis
Sporadic inclusion body myositis (sIBM) is a neurodegenerative disorder that results in progressive limb muscle weakness with bulbar and respiratory involvement. The leading cause of morbidity and mortality are secondary to bulbar dysfunction. The IBMFRS is a reliable patient reported outcome measure used in sIBM, however, we lack objective scales that can quantitate deterioration in bulbar function in a clinic setting. We are conducting a prospective study to test the feasibility of using,and validate the use of the modified oculobulbar facial respiratory score (mOBFRS) in sIBM. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: N. Araujo, M. Wencel, E. Medina, L. Zhang, D. Nguyen, A. Habib, T. Mozaffar, N. Goyal Source Type: research

P.04Resistance exercises with blood flow restriction in patients with sporadic inclusion body myositis
Sporadic inclusion body myositis (sIBM) is the most common muscle disease affecting older adults with no disease-modifying treatment. Resistance exercises increase muscle hypertrophy, but weakness prevents exercising with higher resistance. In healthy subjects, augmentation of light-load training with blood flow restriction improved muscle strength; and similar exercises were safe in the elderly. We therefore investigate whether resistance exercises with blood flow restriction is safe and helpful in sIBM patients. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: C. Liang, M. Burk, A. Wall, H. Wong, L. Augustine, S. Bright, W. Brown, A. Harris, S. Holmes, S. Jeyalingam, S. Large, S. Mai, E. Raper, P. Wong, R. Davis, C. Sue, B. Lucas Source Type: research

P.02Phase 2/3 study of Arimoclomol in sporadic inclusion body myositis: study design
Sporadic inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy occurring in patients over the age of 45 years. IBM muscle displays both inflammatory and degenerative features, yet immune suppression has proven to be ineffective. Modulating the cytoprotective "heat shock response" (HSR) represents a therapeutic strategy targeting both inflammation and degeneration. Arimoclomol is an orally administered pharmacological agent that can up-regulate the HSR by amplifying heat shock protein expression. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: P. Machado, R. Barohn, M. McDermott, T. Blaetter, T. Lloyd, A. Shaibani, M. Freimer, A. Amato, E. Ciafaloni, T. Burns, T. Mozaffar, S. Gibson, M. Wicklund, D. Saperstein, T. Levine, C. Sundgreen, A. Aaes-J ørgensen, T. Liu, L. Herbelin, M. Hanna, M. Dima Source Type: research

Inflammatory myopathies
Recently, growing evidences suggest that approximately 33-80% of patients with sporadic inclusion body myositis (sIBM) have autoantibodies against cytosolic 5 ′-nucleotidase 1A (cN1A). Although the pathogenic role of anti-cN1A autoantibodies has not been fully investigated, our passive immunization model demonstrated upregulation of p62 level as well as downregulation of cN1A level in the muscle specimen of anti-cN1A-positive sIBM IgG-injected mice. To figure out the pathogenic role of anti-cN1A autoantibodies, we investigated the differences in clinicopathological features between sIBM patients with and without anti...
Source: Neuromuscular Disorders - October 1, 2019 Category: Neurology Authors: S. Yamashita, N. Tawara, T. Ikeda, K. Hara, Z. Zhang, X. Zhang, T. Doki, Y. Ando Source Type: research

Interferon-signature in idiopathic inflammatory myopathies
Purpose of review The present review describes the interferon (IFN)-signature currently emerging as a tool for the diagnosis of idiopathic inflammatory myopathies (IIMs), and aims at presenting the interests and limitations of this recent tool for the clinics and the research. Recent findings Recent in-vivo and in-vitro transcriptomic studies have evidenced the involvement of IFNs in the pathogenesis of IIMs. A correlation between the IFN-signature and the clinical severity of IIMs has been established. Moreover, studies pointed out differences in the IFN-signature regarding the IIM subgroup (dermatomyositis, polymyos...
Source: Current Opinion in Rheumatology - September 25, 2019 Category: Rheumatology Tags: MYOSITIS AND MYOPATHIES: Edited by Andrea Doria, Anna Ghirardello, and Mariele Gatto Source Type: research

Diversified Application of Barcoded PLATO (PLATO-BC) Platform for Identification of Protein Interactions
In this report, we tested the antisera-antigen interaction using serum samples from patients with inclusion body myositis (IBM). Tripartite motif containing 21 (TRIM21) was identified as a potentially new IBM autoantigen. We also expanded the application of PLATO-BC to identify protein interactions for JQ1, single ubiquitin peptide, and NS5 protein of Zika virus. From PLATO-BC analyses, we identified new protein interactions for these “bait” molecules. We demonstrate that Ewing sarcoma breakpoint region 1 (EWSR1) binds to JQ1 and their interactions may interrupt the EWSR1 association with acetylated histone H4....
Source: Genomics, Proteomics and Bioinformatics - September 6, 2019 Category: Bioinformatics Source Type: research

A novel case of inclusion body myositis and myasthenia gravis
Myasthenia gravis (MG) is an autoimmune disorder caused by antibodies targeting the neuromuscular junction, which in most cases are directed towards the skeletal muscle acetylcholine receptor (AChR) [1]. The pathophysiology of MG is accepted to be immune mediated [2]. Sporadic inclusion body myositis (IBM) is considered the most common inflammatory myopathy in patients over 50 years old, but its pathophysiology remains to this day an enigma: It is still unclear whether it is a primary degenerative disease with secondary dysimmune reaction or vice versa [3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2019 Category: Neurology Authors: Sakis Lambrianides, Evgenios Kinnis, Michele Cleanthous, Revekka Papacharalambous, Elena Panayiotou, Eleni Zamba-Papanicolaou, Theodoros Kyriakides Tags: Case report Source Type: research

Classification of idiopathic inflammatory myopathies: pathology perspectives
Purpose of review Idiopathic inflammatory myopathies (IIM) are rare diseases with heterogenous clinicopathological features. In recent years, new classification systems considering various combinations of clinical, serological, and pathological information have been proposed. This review summarizes recent clinicoseropathological development in major subgroups of IIM. Recent findings Considering clinicoseropathological features, IIM are suggestively classified into four major subgroups: dermatomyositis, immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASS), and inclusion body myositis (IBM). Many h...
Source: Current Opinion in Neurology - August 29, 2019 Category: Neurology Tags: NEUROMUSCULAR DISEASE: Edited by Michio Hirano Source Type: research

Inclusion body myositis: accumulation of evidence for its autoimmune origin
This scientific commentary refers to ‘Highly differentiated cytotoxic T cells in inclusion body myositis’, by Greenberget al. (doi:10.1093/brain/awz207). (Source: Brain)
Source: Brain - August 29, 2019 Category: Neurology Source Type: research

Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial
Publication date: September 2019Source: The Lancet Neurology, Volume 18, Issue 9Author(s): Michael G Hanna, Umesh A Badrising, Olivier Benveniste, Thomas E Lloyd, Merrilee Needham, Hector Chinoy, Masashi Aoki, Pedro M Machado, Christina Liang, Katrina A Reardon, Marianne de Visser, Dana P Ascherman, Richard J Barohn, Mazen M Dimachkie, James A L Miller, John T Kissel, Björn Oskarsson, Nanette C Joyce, Peter Van den Bergh, Jonathan BaetsSummaryBackgroundInclusion body myositis is an idiopathic inflammatory myopathy and the most common myopathy affecting people older than 50 years. To date, there are no effective drug t...
Source: The Lancet Neurology - August 8, 2019 Category: Neurology Source Type: research

Endpoint choice for inclusion body myositis: a step too far?
Publication date: September 2019Source: The Lancet Neurology, Volume 18, Issue 9Author(s): Jens Schmidt (Source: The Lancet Neurology)
Source: The Lancet Neurology - August 8, 2019 Category: Neurology Source Type: research

Highly differentiated cytotoxic T cells in inclusion body myositis
We examined inclusion body myositis muscle T-cell proliferation by Ki67 immunohistochemistry demonstrating that diseased muscle-invading T cells are minimally or non-proliferative, in accordance with known properties of highly differentiated or terminally differentiated T cells. We found low expression of KLRG1 on infection-protective human lymphoid tissue central memory T cells and autoimmune-protective human blood regulatory T cells. Targeting highly differentiated cytotoxic T cells could be a favourable approach to treatment of inclusion body myositis. (Source: Brain)
Source: Brain - July 20, 2019 Category: Neurology Source Type: research

Development of Autoimmune Interstitial Lung Disease in a Patient with Inclusion Body Myositis
(Source: The American Journal of Medicine)
Source: The American Journal of Medicine - July 13, 2019 Category: General Medicine Authors: Christophe He, Joyce Lee, Carlyne Cool, Matthew Wicklund, Aryeh Fischer Tags: Clinical Communication to the Editor Source Type: research

A family with limb girdle muscular dystrophy type 1B and multiple exostoses.
DISCUSSION: The clinical, genetic, and muscle biopsy findings suggest that both mutations are pathogenic. The EXT2 mutation was most likely responsible for the multiple exostoses phenotype in mother and son, whereas the myopathy was probably caused by a combined effect of the LMNA and EXT2 mutations.
. PMID: 31296281 [PubMed - as supplied by publisher] (Source: Clinical Neuropathology)
Source: Clinical Neuropathology - July 12, 2019 Category: Pathology Authors: Romeike BFM, Becker K, Großkreutz J, Schulz S, Weis J, Cirak S Tags: Clin Neuropathol Source Type: research

Sporadic inclusion body myositis: Diagnostic value of p62 immunostaining.
CONCLUSIONS: Probably p62 immunostaining could help to distinguish PM patients that are going to become sIBM, but to date there has been no systematic study to clarify p62 utility in myositis. PMID: 31253480 [PubMed - as supplied by publisher] (Source: Medicina Clinica)
Source: Medicina Clinica - July 1, 2019 Category: General Medicine Tags: Med Clin (Barc) Source Type: research

The updated retrospective questionnaire study of sporadic inclusion body myositis in Japan
Sporadic inclusion body myositis (sIBM) is the most prevalent muscle disease in elderly people, affecting the daily activities. sIBM is progressive with unknown cause and without effective treatment. In 2015, ... (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - June 26, 2019 Category: Internal Medicine Authors: Naoki Suzuki, Madoka Mori-Yoshimura, Satoshi Yamashita, Satoshi Nakano, Ken-ya Murata, Megumi Mori, Yukie Inamori, Naoko Matsui, En Kimura, Hirofumi Kusaka, Tomoyoshi Kondo, Hidefumi Ito, Itsuro Higuchi, Akihiro Hashiguchi, Hiroyuki Nodera, Ryuji Kaji & h Tags: Research Source Type: research

Disability in idiopathic inflammatory myopathies: questionnaire-based study
AbstractIdiopathic inflammatory myopathies (IIM) are progressive, debilitating diseases that can lead to severe impairment. The aim of the study was to evaluate the level of disability and compare it between different subtypes of IIM as well as to estimate clinical symptoms associated with greater risk of disability and distinguish the most troublesome activities in this group of patients. A online form concerning clinical symptoms, comorbidities and limitations in daily living was created and distributed to online support groups for patients with IIM. Health Assessment Questionnaire was used to estimate disability and phy...
Source: Rheumatology International - June 12, 2019 Category: Rheumatology Source Type: research

Trial of canakinumab, an IL-1{beta} receptor antagonist, in patients with inclusion body myositis
Conclusions In this long-term, open-label study, canakinumab showed small, but not clinically appreciable, stabilizing benefits in 2 of 5 patients with sIBM over 1 year, was ineffective in 2 others, and might have worsened one. No patient improved. Classification of evidence This study provides Class IV evidence that canakinumab was ineffective for patients with sIBM. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - June 10, 2019 Category: Neurology Authors: Kosmidis, M. L., Pikazis, D., Vlachoyiannopoulos, P., Tzioufas, A. G., Dalakas, M. C. Tags: All Immunology, Muscle disease, Clinical trials Observational study (Cohort, Case control), Class IV Article Source Type: research

Pattern of muscle involvement in inclusion body myositis: a sonographic study.
Authors: Albayda J, Christopher-Stine L, Bingham Iii CO, Paik JJ, Tiniakou E, Billings S, Uy OM, Burlina P PMID: 31111821 [PubMed - in process] (Source: Clinical and Experimental Rheumatology)
Source: Clinical and Experimental Rheumatology - May 23, 2019 Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research

Spontaneous Restoration of Nutrition Autonomy in a Case of Intestinal Failure Secondary to a Gastrointestinal Neuromuscular Disease.
Abstract Polyglucosan inclusion body myopathy (PIBM) is a recently described gastrointestinal neuromuscular disease. Given its rarity, very little is known of its natural history and prognosis. In this case report, we present the first case of PIBM and resultant intestinal failure in which, following 7 years of home parenteral nutrition, gastrointestinal symptoms subsided and nutrition autonomy was restored. PMID: 31074888 [PubMed - as supplied by publisher] (Source: Nutrition in Clinical Practice)
Source: Nutrition in Clinical Practice - May 10, 2019 Category: Nutrition Authors: McCulloch A, Malhi H, Parkinson S, Martin JE, Cooper SC Tags: Nutr Clin Pract Source Type: research

Polymyositis with mitochondrial pathology or atypical form of sporadic inclusion body myositis: case series and review of the literature
AbstractPolymyositis with mitochondrial pathology (PM-Mito) is a rare form of idiopathic inflammatory myopathy with no definite diagnostic criteria and similarities to both PM and sporadic inclusion body myositis (s-IBM). The aim of this study is to address the dilemma of whether PM-Mito is a subtype of inflammatory myopathy or represents a disease falling into the spectrum of s-IBM. Herein, we report four female patients diagnosed with PM-Mito, highlighting their rather atypical clinical and histopathological characteristics that seem to indicate a diagnosis away from s-IBM. Muscle weakness was rather proximal and symmetr...
Source: Rheumatology International - May 4, 2019 Category: Rheumatology Source Type: research

HTLV-1 HBZ Protein Resides Exclusively in the Cytoplasm of Infected Cells in Asymptomatic Carriers and HAM/TSP Patients
In conclusion, we believe that the data presented in this research add new relevant information for a better definition of the pathological states associated with HTLV-1 infection, particularly in relation to the distinct subcellular expression of HBZ in the different pathological contests and related pathologies. Whether HBZ cytoplasmic and nuclear localization in the natural history of HTLV-1 infection represents a marker of infection or is part of the mechanism governing the evolution toward HAM/TSP or ATL is the challenge for future investigation. Author Contributions GF, MB, and RA conceived the work. GF, MB, and AT...
Source: Frontiers in Microbiology - April 26, 2019 Category: Microbiology Source Type: research

Inclusion Body Myositis Mimicking Bilateral Anterior Interosseous Neuropathies
We describe 2 patients who initially presented for orthopedic evaluation for suspected anterior interosseous neuropathy and were subsequently diagnosed with inclusion body myositis, an uncommon inflammatory myopathy affecting adults, with a predilection for finger and thumb flexor muscles. (Source: The Journal of Hand Surgery)
Source: The Journal of Hand Surgery - April 25, 2019 Category: Surgery Authors: Elizabeth A. Mauricio, Devon I. Rubin Tags: Case repository Source Type: research

Scurfy Mice Develop Features of Connective Tissue Disease Overlap Syndrome and Mixed Connective Tissue Disease in the Absence of Regulatory T Cells
Osman K. Yilmaz1, Stefanie Haeberle1, Meifeng Zhang1, Marvin J. Fritzler2, Alexander H. Enk1 and Eva N. Hadaschik1,3* 1Department of Dermatology, University of Heidelberg, Heidelberg, Germany 2Mitogen Advanced Diagnostics Laboratory, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada 3Department of Dermatology, University Hospital of Essen, Essen, Germany Due to a missense mutation in the Foxp3 gene, scurfy mice are deficient in functional regulatory T cells (Treg). The consequent loss of peripheral tolerance manifests itself by fatal autoimmune mediated multi-organ disease. Previous studies...
Source: Frontiers in Immunology - April 24, 2019 Category: Allergy & Immunology Source Type: research

PD1 pathway in immune-mediated myopathies: Pathogenesis of dysfunctional T cells revisited
Conclusion Persistent exposure to antigens in IMNMs and sIBM may lead to T-cell exhaustion, a process controlled by the PD1 receptor and its cognate ligands PD-L1/PD-L2. To our knowledge, these data are the first evidence of presence of dysfunctional T cells and relevance of the PD1 pathway in IMNM, sIBM, and irMyositis. These findings may guide the way to a novel understanding of the immune pathogenesis of immune-mediated myopathies. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - April 10, 2019 Category: Neurology Authors: Knauss, S., Preusse, C., Allenbach, Y., Leonard-Louis, S., Touat, M., Fischer, N., Radbruch, H., Mothes, R., Matyash, V., Böhmerle, W., Endres, M., Goebel, H.-H., Benveniste, O., Stenzel, W. Tags: All Immunology, All Neuromuscular Disease, Chemotherapy-tumor Article Source Type: research

Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis
The objectives of our study were to determine the sensitivity and specificity of anti-NT5c1A for sIBM, demonstrate demographic, clinical and serological predictors for anti-NT5c1A positivity and determine if anti-nuclear antibody (ANA) indirect immunofluorescence (IIF) staining on HEp-2 cells is a reliable screening method for anti-NT5c1A. Methods: Sera from sIBM patients and controls were stored at −80°C until required for analysis. IgG antibodies to NT5c1A were detected by an addressable laser bead immunoassay (ALBIA) using a full-length human recombinant protein. Autoantibodies to other autoimmune myopathy an...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

ULK1 and ULK2 Regulate Stress Granule Disassembly Through Phosphorylation and Activation of VCP/p97
Wang et  al. demonstrate that the autophagy-inducing kinases ULK1 and ULK2 regulate stress granule disassembly by phosphorylating and activating the AAA+ ATPase VCP. Defects in this pathway contribute to the development of inclusion body myopathy-like disease in mice. (Source: Molecular Cell)
Source: Molecular Cell - April 9, 2019 Category: Cytology Authors: Bo Wang, Brian A. Maxwell, Joung Hyuck Joo, Youngdae Gwon, James Messing, Ashutosh Mishra, Timothy I. Shaw, Amber L. Ward, Honghu Quan, Sadie Miki Sakurada, Shondra M. Pruett-Miller, Tulio Bertorini, Peter Vogel, Hong Joo Kim, Junmin Peng, J. Paul Taylor, Tags: Article Source Type: research

Cardiac Manifestations in Idiopathic Inflammatory Myopathies: An Overview
Idiopathic inflammatory myopathies are a group of autoimmune diseases that are characterized by muscle inflammation resulting in elevated muscle enzyme release and distinctive biopsy findings. This group of conditions includes polymyositis, dermatomyositis, inclusion body myositis, and necrotizing autoimmune myopathy. Although they have many similarities, the inflammatory myopathies differ in their clinical, pathological, and treatment realms. Extramuscular manifestations may involve many organs that include the skin, joints, heart, lungs, and gastrointestinal tract. Cardiovascular involvement is one of the leading causes ...
Source: Cardiology in Review - April 6, 2019 Category: Cardiology Tags: Review Articles Source Type: research

Distal myopathy and rapidly progressive dementia associated with a novel mutation in the VCP gene: Expanding inclusion body myopathy with early-onset Paget disease and frontotemporal dementia spectrum
We report a severe phenotype in a Portuguese patient, related to a novel mutation in the valosin-containing protein gene, characterized by a severe late-onset distal myopathy and a rapidly progressive cognitive dysfunction suggesting fronto-temporal dementia. The patient did not manifest Paget disease. Family history was negative. This case emphasizes the importance of considering inclusion body myopathy with early-onset Paget disease and fronto-temporal dementia in the differential diagnosis of distal myopathies, even in the absence of family history. (Source: Journal of Clinical Neuroscience)
Source: Journal of Clinical Neuroscience - April 5, 2019 Category: Neuroscience Source Type: research

The Blastomycosis Bluff by Purpureocillium lilacinum
A 73-year-old patient with a history of rheumatoid arthritis and inclusion body myositis on long-term prednisone and azathioprine presented with a 3-month history of tender erythematous nodules on his right lower extremity (Figure  1). A skin biopsy revealed yeast forms with broad-based budding yeast (Figure 2, [arrow]). Initially, a diagnosis of cutaneous blastomycosis was made, and he was initiated on itraconazole. However, (1-3)-β-d-glucan assay was elevated at>500 pg/mL (reference range: (Source: Mayo Clinic Proceedings)
Source: Mayo Clinic Proceedings - April 1, 2019 Category: Internal Medicine Authors: Zachary T. Lundstrom, Omar M. Abu Saleh Tags: Medical images Source Type: research

Motor unit potential changes in myofibrillar myopathy
Both conventional and quantitative electromyography (Q-EMG) studies have been conducted in relatively large samples in common myopathies such as muscle dystrophies, inflammatory myopathies and mitochondrial myopathies [1,2]. These studies report a rather modest diagnostic sensitivity, with lowest sensitivity values found in mitochondrial myopathies [3]. In contrast, motor unit action potential (MUP) analysis appears very sensitive in sporadic inclusion body myositis, where a decreased mean duration is observed in 94% of the patients [4]. (Source: Journal of the Neurological Sciences)
Source: Journal of the Neurological Sciences - March 20, 2019 Category: Neurology Authors: E. Anagnostou, I. Vasilakou, C. Papadopoulos, T. Zambelis, G. Papadimas Tags: Letter to the Editor Source Type: research

A Patient with Sjogren ’s Syndrome and Subsequent Diagnosis of Inclusion Body Myositis and Light-Chain Amyloidosis
AbstractWe discuss a challenging case of a 58-year-old Vietnamese-American woman who presented to her new primary care provider with an 8-year history of slowly progressive dysphagia, hoarseness, muscle weakness with associated frequent falls, and weight loss. She eventually reported dry eyes and dry mouth, and she was diagnosed with Sjogren ’s syndrome. Subsequently, she was additionally diagnosed with inclusion body myositis and gastric light-chain (AL) amyloidosis. Although inclusion body myositis has been previously associated with Sjogren’s syndrome, inclusion body myositis is rare in non-Caucasians, and t...
Source: Journal of General Internal Medicine - March 18, 2019 Category: Internal Medicine Source Type: research

18F-FDG PET/CT versus conventional investigations for cancer screening in autoimmune inflammatory myopathy in the era of novel myopathy classifications
Conclusion 18F-FDG PET/CT does not appear to be useful in cancer screening for AIM patients compared with conventional screening and carries potential harms associated with follow-up investigations. The risk of cancer in AIM differs by myositis-specific antibodies-defined subsets and cancer screening is likely to be indicated only in high-risk patients, particularly DM. These results, replicated in larger, multicentered studies, may carry significant consequences for optimal management of AIM and health resource utilization. (Source: Nuclear Medicine Communications)
Source: Nuclear Medicine Communications - March 16, 2019 Category: Nuclear Medicine Tags: ORIGINAL ARTICLES Source Type: research

Myalgia with the presence of pathologic EMG correlates with perimysial inflammatory infiltrates
Conclusions Normal muscle contains a considerable number of macrophages and T-lymphocytes. Muscle biopsy is likely to detect inflammatory changes in patients with myalgia or hyperCKemia only if pathologic EMG findings are present. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - March 11, 2019 Category: Neurology Authors: Johannssen, K., Schwab, N., Wessig, C. P., Reiners, K., Wiendl, H., Sommer, C. Tags: Autoimmune diseases, Muscle disease, EMG Article Source Type: research

Coexistence of anti-Jo1 and anti-signal recognition particle antibodies in a polymyositis patient
We present a man with polymyositis who had both antibodies in serum, which is considered an extremely rare clinical situation. Here we analyse the clinical course and findings, and examine the effect of the coexistence and possible interaction on prognosis.ResumenLas miopatías inflamatorias idiopáticas son un grupo heterogéneo de miopatías potencialmente tratables. Se clasifican en 4 subtipos: dermatomiositis, polimiositis, miositis autoinmune necrosante y miositis por cuerpos de inclusión, en función de las características clínicas e histológicas. Los anticuer...
Source: Reumatologia Clinica - March 9, 2019 Category: Rheumatology Source Type: research

CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis
ConclusionUsing a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease. (Source: Autoimmunity Reviews)
Source: Autoimmunity Reviews - March 9, 2019 Category: Allergy & Immunology Source Type: research

Muscle fiber dysfunction contributes to weakness in inclusion body myositis
Sporadic inclusion body myositis (IBM) is one of the most common acquired muscle disorders in adults over 50 years old [1,2]. Progressive disease is characterized by atrophy and fatty infiltration of muscle tissue, resulting in muscle weakness [3 –5]. In early disease, the quadriceps, deep finger flexors and the pharyngeal muscles are most frequently affected, restricting functional ability and quality of life [6–8]. IBM is the result of a complex and only partially understood interplay between muscle inflammation, degeneration and impai red proteostasis which results in the accumulation of proteins in rimmed v...
Source: Neuromuscular Disorders - March 6, 2019 Category: Neurology Authors: Saskia Lassche, Anke Rietveld, Arend Heerschap, Hieronymus W van Hees, Maria TE Hopman, Nicol C Voermans, Christiaan GJ Saris, Baziel GM van Engelen, Coen AC Ottenheijm Source Type: research