Congenital Myopathy with Abundant Ring Fibres, Rimmed Vacuoles and Inclusion Body Myositis-Type Inclusions

2003 ◽  
Vol 34 (1) ◽  
pp. 40-44 ◽  
Author(s):  
A. Fidziańska ◽  
A. Kamińska
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Congenital Myopathy ◽  
Rimmed Vacuoles

Coexistence of TDP-43 and C5b-9 staining of muscle in a patient with inclusion body myositis

2021 ◽  
Vol 14 (2) ◽  
pp. e238312
Author(s):  
Christina Law ◽  
Huili Li ◽  
Sankar Bandyopadhyay
Keyword(s):  
Inclusion Body ◽  
Transcriptional Repression ◽  
Inclusion Body Myositis ◽  
Inflammatory Myopathy ◽  
Membrane Attack Complex ◽  
Muscle Fibres ◽  
Rimmed Vacuoles ◽  
Histocompatibility Complex ◽  
Immune Mediated ◽  
Sporadic Inclusion Body Myositis

While sporadic inclusion body myositis (sIBM) is the most commonly acquired inflammatory myopathy above 50 years of age, its refractory response to conventional immunosuppressive treatments raises questions about its perplexing pathogenesis. Muscle biopsy typically reveals major histocompatibility complex I antigens and CD8+ T cell endomysial infiltrates invading non-necrotic muscle fibres early in the disease course with rimmed vacuoles, protein aggregates and amyloid inclusions later in the disease. Transactive response DNA-binding protein-43 (TDP-43), a protein implicated in transcriptional repression in neurodegenerative diseases, is also found in sIBM. C5b-9 membrane attack complex, an effector protein involved in the complement cascade of the immune response, is commonly found in dermatomyositis, but has rarely been reported in IBM. We describe a novel case of IBM with simultaneous C5b-9 and TDP-43 staining on quadriceps biopsy, raising the question of a possibility of concurrent immune-mediated inflammatory and myodegenerative pathogenesis.

Bcl-2, Bcl-x, and Bax Expression by Immunohistochemistry in Inclusion Body Myositis

2001 ◽  
Vol 125 (10) ◽  
pp. 1326-1330
Author(s):  
Richard A. Prayson ◽  
Albert C. Yu
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Staining Pattern ◽  
Apoptotic Cell ◽  
Muscle Fibers ◽  
Inflammatory Cells ◽  
Rimmed Vacuoles ◽  
Autophagic Vacuoles ◽  
Ultrastructural Evidence ◽  
Mitochondrial Defects

Abstract Context.—Bcl-2, Bcl-x, and Bax are among the variety of proteins that have been described as being involved in the regulation of apoptotic cell death. Bcl-2 and Bcl-xL inhibit apoptosis, and Bax is proapoptotic. Objective.—To evaluate the expression of Bcl-2, Bcl-x, and Bax in inclusion body myositis (IBM). Design.—We examined muscle specimens from 27 patients (17 men, 10 women) with IBM to evaluate Bcl-2, Bcl-x, and Bax expression by immunohistochemistry. Results.—Patient ages ranged from 29 to 80 years (mean 62.2 years). All biopsies were marked by endomysial chronic inflammation, muscle fiber necrosis, and regeneration. Rimmed (autophagic) vacuoles were present in all cases. Ragged red fibers were noted in 4 biopsies (15%), and cytochrome oxidase–deficient fibers were found in 10 biopsies (37%). Ultrastructural evidence of intranuclear or cytoplasmic tubulofilamentous inclusions, confirming the diagnosis of IBM, were noted in all cases. Paracrystalline mitochondrial inclusions were seen in 5 biopsies (18.5%). Inflammatory cells stained positively with Bcl-2 in all biopsies, Bax in 26 biopsies (96%), and Bcl-x in 8 biopsies (30%). Degenerating muscle fibers were highlighted with Bax in 24 biopsies (89%), Bcl-2 in 2 biopsies (7%), and Bcl-x in 3 biopsies (11%). Regenerative muscle fibers were noted to stain with Bax in 24 muscles (89%), Bcl-2 in 21 muscles (78%), and Bcl-x in 4 muscles (15%). Rimmed vacuoles were highlighted by Bax in 24 biopsies (89%) and only rarely by Bcl-2 (n = 2, 7%) and Bcl-x (n = 3, 11%). A subsarcolemmal staining pattern was observed in 21 biopsies (78%) with Bax, 6 biopsies (22%) with Bcl-2, and only 1 biopsy (4%) with Bcl-x. Conclusions.—(1) Bax (proapoptotic) immunostaining highlighted most autophagic vacuoles; (2) subsarcolemmal Bax and Bcl-2 immunoreactivity may be associated with mitochondrial defects that are commonly noted in IBM; (3) Bcl-2 and Bax immunoreactivity were not confined to degenerating muscle fibers and in fact appeared to be expressed more commonly in regenerating fibers, suggesting that their expression may be independent of apoptosis in the setting of IBM.

scholarly journals Familial Inclusion Body Myositis (FIBM)

2019 ◽  
Vol 17 (2) ◽  
pp. 193-195
Author(s):  
Marco Orsini ◽  
Mariana Pimentel Mello ◽  
Marcos RG de Freitas ◽  
Osvaldo JM Nascimento
Keyword(s):  
Creatine Kinase ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Inflammatory Cell ◽  
Late Onset ◽  
Serum Creatine Kinase ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Rimmed Vacuoles ◽  
Sporadic Inclusion Body Myositis

Familial inclusion body myositis (FIBM) is extremely rare. The disease is characterized by relatively late onset, selective and early involvement of quadriceps, forearm and finger flexors, only mild increase of serum creatine kinase CK level, frequent rimmed vacuoles in muscle histopathology with substantial inflammatory cell infiltration. The combination of clinical, histological, immunopathological and immunogenetic features indicates that these patients have a disease identical to sporadic inclusion body myositis.

scholarly journals Proteomics of rimmed vacuoles define new risk allele in inclusion body myositis

2017 ◽  
Vol 81 (2) ◽  
pp. 227-239 ◽  
Author(s):  
Anne-Katrin Güttsches ◽  
Stefen Brady ◽  
Kathryn Krause ◽  
Alexandra Maerkens ◽  
Julian Uszkoreit ◽  
...  
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Risk Allele ◽  
Rimmed Vacuoles

scholarly journals Inclusion-Body Myositis Associated with Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Danijela Levacic ◽  
Leema Reddy Peddareddygari ◽  
David Nochlin ◽  
Leroy R. Sharer ◽  
Raji P. Grewal
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Tau Proteins ◽  
Muscle Pathology ◽  
Rimmed Vacuoles ◽  
Pathologic Features ◽  
Sporadic Inclusion Body Myositis ◽  
Progressive Weakness

Sporadic inclusion-body myositis (s-IBM) is a myopathy that is characterized by progressive weakness and muscle pathology demonstrating inflammation and rimmed vacuoles. In addition, similar to the pathology observed in the brains of patients with Alzheimer’s disease, the deposition of beta-amyloid and phosphorylated tau proteins in muscle fibers has been reported. These shared pathologic features have prompted hypotheses suggesting a shared etiology of these two conditions. We report a case of a 73-year-old woman initially diagnosed with s-IBM who later developed Alzheimer’s disease.

scholarly journals Overlapping features of polymyositis and inclusion body myositis in HIV-infected patients

Neurology ◽  
2017 ◽  
Vol 88 (15) ◽  
pp. 1454-1460 ◽  
Author(s):  
Thomas E. Lloyd ◽  
Iago Pinal-Fernandez ◽  
E. Harlan Michelle ◽  
Lisa Christopher-Stine ◽  
Katherine Pak ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Inclusion Body ◽  
Muscle Biopsy ◽  
Inclusion Body Myositis ◽  
Age At Onset ◽  
Case Series ◽  
Knee Extensors ◽  
Hiv Positive ◽  
Rimmed Vacuoles ◽  
The Mean

Objective:To characterize patients with myositis with HIV infection.Methods:All HIV-positive patients with myositis seen at the Johns Hopkins Myositis Center from 2003 to 2013 were included in this case series. Muscle biopsy features, weakness pattern, serum creatine kinase (CK) level, and anti–nucleotidase 1A (NT5C1A) status of HIV-positive patients with myositis were assessed.Results:Eleven of 1,562 (0.7%) patients with myositis were HIV-positive. Myositis was the presenting feature of HIV infection in 3 patients. Eight of 11 patients had weakness onset at age 45 years or less. The mean time from the onset of weakness to the diagnosis of myositis was 3.6 years (SD 3.2 years). The mean of the highest measured CK levels was 2,796 IU/L (SD 1,592 IU/L). On muscle biopsy, 9 of 10 (90%) had endomysial inflammation, 7 of 10 (70%) had rimmed vacuoles, and none had perifascicular atrophy. Seven of 11 (64%) patients were anti-NT5C1A-positive. Upon presentation, all had proximal and distal weakness. Five of 6 (83%) patients followed 1 year or longer on immunosuppressive therapy had improved proximal muscle strength. However, each eventually developed weakness primarily affecting wrist flexors, finger flexors, knee extensors, or ankle dorsiflexors.Conclusions:HIV-positive patients with myositis may present with some characteristic polymyositis features including young age at onset, very high CK levels, or proximal weakness that improves with treatment. However, all HIV-positive patients with myositis eventually develop features most consistent with inclusion body myositis, including finger and wrist flexor weakness, rimmed vacuoles on biopsy, or anti-NT5C1A autoantibodies.

scholarly journals Clinical, Histological, and Immunohistochemical Findings in Inclusion Body Myositis

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Leonardo Valente de Camargo ◽  
Mary Souza de Carvalho ◽  
Samuel Katsuyuki Shinjo ◽  
Acary Souza Bulle de Oliveira ◽  
Edmar Zanoteli
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Immunosuppressive Treatment ◽  
Clinical Manifestations ◽  
Lower Limbs ◽  
Histological Findings ◽  
Rimmed Vacuoles ◽  
Amyloid Accumulation ◽  
Sporadic Inclusion Body Myositis ◽  
Muscle Biopsies

Sporadic inclusion body myositis (sIBM) is considered the most common acquired myopathy aged over 50 years. The disease is characterized by a particular process of muscle degeneration characterized by abnormal deposit of protein aggregates in association with inflammation. The aim of this study was to present clinical and muscle histopathological findings, including immunostaining for LC3B, p62, α-synuclein, and TDP-43, in 18 patients with sIBM. The disease predominated in males (61%) and European descendants, with onset of clinical manifestations around 59 years old. The most common symptoms were muscle weakness, falls, dysphagia, and weight loss. Hypertension was the main comorbidity. Most of the cases presented with paresis predominantly proximal in lower limbs and distal in upper limbs. Immunosuppressive treatment showed to be not effective. Muscle histological findings included dystrophic changes, endomysial inflammation, increased lysosomal activity, and presence of rimmed vacuoles and of beta-amyloid accumulation, in addition to high frequency of mitochondrial changes. There was increased expression of LC3B, p62, α-synuclein, and TDP-43 in muscle biopsies. The sIBM has characteristic clinical and histological findings, and the use of degeneration and autophagic markers can be useful for the diagnosis.

Histone H1 is released from myonuclei and present in rimmed vacuoles with DNA in inclusion body myositis

2008 ◽  
Vol 18 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Satoshi Nakano ◽  
Akiyo Shinde ◽  
Kengo Fujita ◽  
Hidefumi Ito ◽  
Hirofumi Kusaka
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Histone H1 ◽  
Rimmed Vacuoles

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

2021 ◽  
Author(s):  
Kyla A. Britson ◽  
Jonathan P. Ling ◽  
Kerstin E. Braunstein ◽  
Janelle M. Montagne ◽  
Jenna M. Kastenschmidt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Xenograft Model ◽  
Muscle Disease ◽  
Mhc I ◽  
Rimmed Vacuoles ◽  
Sporadic Inclusion Body Myositis ◽  
Muscle Biopsies

AbstractSporadic 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 exhibit nuclear clearance and cytoplasmic aggregation of TDP-43 in muscle cells, a pathologic finding observed initially in neurodegenerative disease, and nuclear loss of TDP-43 in neurons causes aberrant RNA splicing. Here, we show that loss of TDP-43 splicing repression, as determined by inclusion of cryptic exons, occurs in skeletal muscle of IBM patients. Out of 119 muscle biopsies tested, RT-PCR-mediated detection of cryptic exon expression is 84% sensitive and 99% specific for diagnosing IBM, indicating utility as a functional and diagnostic biomarker. To determine the role of T cells in pathogenesis, we generated a novel xenograft model by transplanting human IBM muscle into the hindlimb of immunodeficient mice. Xenografts from IBM patients display robust regeneration of human myofibers and recapitulate both inflammatory and degenerative features of the disease. Myofibers in IBM xenografts are invaded by human, oligoclonal CD8+ T cells and exhibit MHC-I upregulation, rimmed vacuoles, mitochondrial pathology, p62-positive inclusions, and nuclear clearance and cytoplasmic aggregation of TDP-43, resulting in expression of cryptic exons. Depletion of human T cells within IBM xenografts by treating mice intraperitoneally with anti-CD3 (OKT3) suppresses MHC-I upregulation, but rimmed vacuoles and loss of TDP-43 function persist. These data suggest that myofiber degeneration occurs independent of T cells, and muscle cell-intrinsic mechanisms, such as loss of TDP-43 splicing repression, drive IBM pathogenesis.One Sentence SummaryDepletion of T cells in a xenograft model of sporadic inclusion body myositis suppresses inflammation but not TDP-43 pathology or muscle degeneration.

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