Basement membrane remodelling and segmental fibrosis in sporadic inclusion body myositis

Neuromuscul Disord. 2009 Jun;19(6):406-11. doi: 10.1016/j.nmd.2009.04.011. Epub 2009 May 26.

Abstract

Sporadic inclusion body myositis (sIBM) is a debilitating idiopathic inflammatory myopathy. Little is known about the pathogenetic mechanisms that lead to myofiber degeneration. In the present study, we evaluated the integrity of the myofiber basement membrane in non-necrotic myofibers invaded by inflammatory infiltrates. We used 100 ten mum thick serial sections obtained from biopsies of 5 patients suffering from sIBM. Biopsies from 5 patients suffering from polymyositis served as controls. We performed sequential HE staining and immunolabeling using anti-CD68, -CD8, -merosin, -laminin alpha4 chain, and -collagen IV antibodies. In sIBM, we detected a total of 89 non-necrotic myofibers that were invaded by inflammatory cells. The invasive process and its sequelae were segmental in nature and included destruction of the myofiber basement membrane, and eventually, partial replacement by fibrosis of the invaded myofiber. In polymyositis, we found only two myofibers that were affected in this way. In sIBM, basement membrane remodelling and irreversible replacement by fibrosis of myofibers appear to represent the end result of a process in which the balance between injury and repair are disrupted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Basement Membrane / immunology*
  • Basement Membrane / metabolism
  • Basement Membrane / pathology*
  • CD8 Antigens / metabolism
  • Collagen / metabolism
  • Creatine Kinase / blood
  • Female
  • Fibrosis
  • Humans
  • Immunohistochemistry
  • Laminin / metabolism
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / immunology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology*
  • Myositis, Inclusion Body / immunology
  • Myositis, Inclusion Body / metabolism
  • Myositis, Inclusion Body / pathology*
  • Polymyositis / pathology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • CD8 Antigens
  • LAMA4 protein, human
  • Laminin
  • Collagen
  • Creatine Kinase