Sporadic inclusion body myositis: Pathogenic considerations

  title={Sporadic inclusion body myositis: Pathogenic considerations},
  author={George Karpati and Erin O'ferrall},
  journal={Annals of Neurology},
Sporadic inclusion body myositis is the commonest acquired disease of skeletal muscles after 50 years of age, and as such it has commanded a great deal of attention of investigators over the past 25 years. As a result, a large amount of information has accumulated concerning its clinical profile, myopathology, and immunopathology. In the myopathology and immunopathology, there is general agreement that the characteristic features could be divided into a degenerative and an inflammatory group… 
Sporadic inclusion body myositis: the genetic contributions to the pathogenesis
This review summarizes the current understanding of the genetic contributions to sIBM and provides some insights for future research in this mysterious disease with the advantage of the rapid development of advanced genetic technology.
Idiopathic Inflammatory Myopathies: A Review of Immunopathological Features and Current Models of Pathogenesis
The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of chronic systemic disorders characterized by muscle inflammation and progressive muscle weakness, and a growing body of evidence suggests that genetically susceptible individuals probably develop an idiopathy in response to particular environmental stimuli.
Idiopathic Inflammatory Myopathies: Clinical Approach and Management
A basic diagnostic approach to patients with suspected IIM is provided, current therapeutic strategies are summarized, and an insight into future prospective therapies is provided.
Inclusion body myositis
  • S. Greenberg
  • Biology, Medicine
    Current opinion in rheumatology
  • 2011
Sporadic inclusion body myositis understanding continues to advance, with progress regarding the mechanism of this disease.
Inclusion Body Myositis
The identification of a B-cell pathway has resulted in the first identification of an IBM autoantigen and emphasized its status as an autoimmune disease, and the recognition that large granular lymphocyte CD8+ T- cell expansions are present in both blood and muscle provides additional biomarkers for IBM and suggests a mechanistic relationship to the neoplastic disease T-cell large granules lymphocytic leukemia.
Inclusion body myositis in the rheumatology clinic
Inclusion body myositis is a rare sporadic inflammatory‐degenerative myopathy of the elderly. Despite being the commonest type of acquired myopathy after the age of 50, misdiagnosis is extremely
Inclusion body myositis in a patient with long standing rheumatoid arthritis treated with anti-TNFα and rituximab
The case of a 57-year-old patient with long standing rheumatoid arthritis who developed muscle wasting and weakness of the quadriceps femoris after initiation of anti-TNFα treatment is presented, underlines the therapeutic difficulties in IBM and suggests that anti- TNFα therapy might even be deleterious.
Sporadic Inclusion Body Myositis: Inflammatory and Degenerative Disease Mechanisms
It was shown that IFN-γ receptor protein expression on myofiber membranes correlated with the extent of inflammatory CD8+ T cell infiltrates surrounding the myofibers, whereas the ubiquitous HLA-I upregulation is triggered further upstream by as-yet-unknown mechanisms.
Theories of the Pathogenesis of Inclusion Body Myositis
  • S. Greenberg
  • Biology, Medicine
    Current rheumatology reports
  • 2010
Specific theories of its pathogenesis are reviewed and general considerations pertaining to modeling of this disease discussed, and the critical role of biomarkers and methodologic issues in their discovery are considered.


Inclusion Body Myositis—A Review
  • H. Vogel
  • Medicine, Biology
    Advances in anatomic pathology
  • 1998
Inclusion body myositis (IBM), a sporadic inflammatory myopathy, is the most frequently occurring progressive myopathy in adults older than 55 years and usually is clinically and pathologically distinguishable from dermatomyositis or polymyositis.
Inclusion-body myositis
It is proposed that the identified abnormal accumulation, misfolding, and aggregation of proteins, perhaps provoked by the aging milieu and aggravated by the oxidative stress, lead to the s-IBM-specific vacuolar degeneration and atrophy of muscle fibers.
Sporadic inclusion body myositis—diagnosis, pathogenesis and therapeutic strategies
  • M. Dalakas
  • Biology, Medicine
    Nature Clinical Practice Neurology
  • 2006
Emerging data imply that continuous upregulation of cytokines and major histocompatibility complex class I on the muscle fibers causes an endoplasmic reticulum stress response, resulting in intracellular accumulation of misfolded glycoproteins and activation of the transcription factor NFκB, leading to further cytokine activation.
Inclusion body myositis and myopathies
Molecular pathology and pathogenesis of inclusion‐body myositis
The basic hypothesis is that overexpression of AβPP within the aging muscle fibers is an early upstream event causing a subsequent pathogenic cascade that leads to sporadic inclusion‐body myositis.
A perspective on sporadic inclusion-body myositis
Diet and inflammation may be useful experimental variations in exploring the pathogenesis of sIBM and various subsets of the usual aging changes in aging brain, muscle, and vessels can be attenuated in rodents by caloric intake and in humans by drugs with anti-inflammatory and anticoagulant activities.
Biologically stressed muscle fibers in sporadic IBM
Investigation of the possible overexpression of αB-crystallin (αBC) in muscle fibers of sIBM patients and in appropriate controls found that immunoreactive αBC was the most prevalent (2.6 to 19% of total fibers) in microscopically normal fibers (“X fibers”).
Inflammatory, immune, and viral aspects of inclusion-body myositis
Muscle biopsies from patients with sporadic inclusion-body myositis (sIBM) consistently demonstrate that the inflammatory T cells almost invariably invade intact (not vacuolated) fibers, whereas the
The pathological diagnosis of specific inflammatory myopathies.
Pathological diagnosis of dermatomyositis, polymyositis (PM), and inclusion body myositis should be possible in almost all cases when an appropriately involved muscle is biopsied, and separate, still less well characterized forms of inflammatory myopathy occur in young children.