Proinflammatory cell stress in sporadic inclusion body myositis muscle: overexpression of αB-crystallin is associated with amyloid precursor protein and accumulation of β-amyloid

I E Muth
December 2009
Journal of Neurology, Neurosurgery & Psychiatry;Dec2009, Vol. 80 Issue 12, p1344
Academic Journal
BACKGROUND: In the pathology of sporadic inclusion body myositis (sIBM), the relevance of cell stress molecules such as the heat shock protein αB-crystallin, particularly in healthy appearing muscle fibres, has remained elusive. METHODS: 10 muscle biopsies from sIBM patients were serially stained for haematoxylin–eosin, trichrome and multi-immunohistochemistry for neural cell adhesion molecule (NCAM), αB-crystallin, amyloid precursor protein (APP), desmin, major histocompatibility complex I, β-amyloid and ubiquitin. Corresponding areas of all biopsies were quantitatively analysed for all markers. Primary myotube cultures were exposed to the proinflammatory cytokines interleukin (IL)-1β and interferon (IFN)-γ. RESULTS: In human myotubes exposed to IL-1β+IFN-γ, overexpression of APP was accompanied by upregulation of αB-crystallin. In sIBM muscle biopsies, over 20% of all fibres displayed accumulation of β-amyloid or vacuoles/inclusions. A clearly larger fraction of the fibres were positive for αB-crystallin or APP. In contrast with the accumulation of β-amyloid in atrophic fibres, a major part of fibres positive for APP or αB-crystallin showed no morphological abnormalities. Expression of APP and αB-crystallin significantly correlated with each other and most double positive fibres displayed accumulation of β-amyloid, vacuoles or an atrophic morphology. In almost all of these fibres, other markers of degeneration/regeneration such as NCAM and desmin were evident as additional indicators of a cell stress response. Some fibres double positive for APP and αB-crystallin displayed infiltration by inflammatory cells. CONCLUSION: Our results suggest that αB-crystallin is associated with overexpression of APP in sIBM muscle and that upregulation of αB-crystallin precedes accumulation of β-amyloid. The data help to better understand early pathological changes and underscore the fact that a network of cell stress, inflammation and degeneration is relevant to sIBM.


Related Articles

  • Analysis of HLA class I and II alleles in sporadic inclusion-body myositis. Lampe, Johannes B.; Gossrau, Gudrun; Kempe, Andrea; Füssel, Monika; Schwurack, Katja; Schröder, Rolf; Krause, Sabine; Kohnen, Ralf; Walter, Maggie C.; Reichmann, Heinz; Lochmüller, Hanns // Journal of Neurology;Nov2003, Vol. 250 Issue 11, p1313 

    Sporadic inclusion body myositis (s-IBM) is characterised by progressive weakness of proximal and distal limb muscles. Most patients are aged over 50 years at disease onset. Muscle biopsy reveals an inflammatory myopathy and cytoplasmic amyloid deposits. The mononuclear infiltrate is dominated...

  • Treatment of inflammatory myopathies. Cordeiro, A.C.; Isenberg, D. A. // Postgraduate Medical Journal;Jul2006, Vol. 82 Issue 969, p417 

    Idiopathic inflammatory myopathies, notably polymyositis and dermatomyositis are comparatively uncommon diseases and few randomised, double blind placebo controlled trials have been done. Final validation of measures to assess outcome and response to treatment is awaited. Corticosteroids are an...

  • Inclusion body myositis - pathomechanism and lessons from genetics. Murnyák, Balázs; Bodoki, Levente; Vincze, Melinda; Griger, Zoltán; Csonka, Tamás; Szepesi, Rita; Andrea Kurucz; Dankó, Katalin; Hortobágyi, Tibor // Open Medicine;2015, Vol. 10 Issue 1, p-1 

    Inclusion body myositis is a rare, late-onset myopathy. Both inflammatory and myodegenerative features play an important role in their pathogenesis. Overlapping clinicopathological entities are the familial inclusion body myopathies with or without dementia. These myopathies share several...

  • Incidence of Malignant Disease in Biopsy-Proven Inflammatory Myopathy. Buchbinder, Rachelle; Forbes, Andrew; Hall, Stephen; Dennett, Xenia; Giles, Graham // Annals of Internal Medicine;06/19/2001, Vol. 134 Issue 12, p1087 

    Studies the risk for malignant disease in patients with biopsy-proven inflammatory myopathies in Australia. Identification of biopsy-positive inflammatory myopathy; Identification of malignant disease and deaths; Incidence ratios for malignant disease associated with diagnosis of myositis.

  • monomyositis.  // Taber's Cyclopedic Medical Dictionary (2009);2009, Issue 21, p1488 

    A definition of the medical term "monomyositis," which refers to the inflammation of a single muscle, is presented.

  • myosclerosis.  // Taber's Cyclopedic Medical Dictionary (2009);2009, Issue 21, p1533 

    A definition of the term "myosclerosis," which refers to hardening of muscle, is presented.

  • Dermatomyositis. Koler, Ric Anthony; Montemarano, Andrew // American Family Physician;11/1/2001, Vol. 64 Issue 9, p1565 

    Dermatomyositis is an idiopathic inflammatory myopathy with characteristic skin manifestations. Although the disorder is rare, with a prevalence of one to10 cases per million in adults and one to 3.2 cases per million in children, early recognition and treatment are important ways to decrease...

  • Patient presents with pain, proptosis, limited motility. Fastenberg, Bruce A.; Chynn, Emil William; Ritch, Robert // Ophthalmology Times;12/15/99, Vol. 24 Issue 24, p12 

    Presents information on orbital myositis. Symptoms and diagnosis; Possible causes; Treatment for disease.

  • Pathophysiological Factors which Determine the Exercise Intolerance in Patients with Juvenile Dermatomyositis. Takken, Tim; Elst, Elisabeth F.; Van der Net, Janjaap // Current Rheumatology Reviews;2005, Vol. 1 Issue 1, p91 

    Juvenile Dermatomyositis (JDM) is one of the idiopathic inflammatory myopathies in childhood. In this disease the immune system targets the microvasculature of the skeletal muscle and skin, leading to myopathy and a typical skin rash. During episodes of active disease patients experience a...


Read the Article


Sign out of this library

Other Topics