The inflammatory reaction pattern distinguishes primary dysferlinopathies from idiopathic inflammatory myopathies: an important role for the membrane attack complex

Acta Neuropathol. 2006 Sep;112(3):325-32. doi: 10.1007/s00401-006-0113-5. Epub 2006 Jul 22.

Abstract

Degenerative muscle changes in dysferlinopathies are often accompanied by inflammatory infiltrates and may even mimic primary idiopathic inflammatory myopathies. In the present study, the inflammatory reaction pattern with respect to the cellular composition of the infiltrates and the expression of potent cytokines was characterized in dysferlinopathies and in idiopathic inflammatory myopathies. Cellular infiltrates in dysferlinopathies mainly consisted of CD4+CD25- T cells and macrophages. We noted a prominent expression of interferon-gamma which may contribute to the marked upregulation of MHC class I antigen observed on the vast majority of muscle fibres. Furthermore, membrane attack complex positive deposits were found on intact as well as necrotic muscle fibres. Collectively, our study indicates that the inflammatory reaction pattern in dysferlinopathies is distinct from the one in idiopathic inflammatory myopathies. In particular, membrane attack complex deposits and a pro-inflammatory milieu in the absence of interleukin-10 expression may contribute to progressive muscle damage in dysferlinopathies.

MeSH terms

  • Blotting, Western
  • CD8 Antigens / metabolism
  • Complement Membrane Attack Complex / metabolism
  • Complement Membrane Attack Complex / physiology*
  • Cytokines / metabolism
  • Diagnosis, Differential
  • Dysferlin
  • Fluorescent Antibody Technique
  • Genes, MHC Class I / genetics
  • Granzymes / metabolism
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Interferon-gamma / biosynthesis
  • Macrophages / pathology
  • Membrane Glycoproteins / biosynthesis
  • Membrane Proteins / genetics*
  • Muscle Proteins / genetics*
  • Muscular Diseases / metabolism
  • Muscular Diseases / pathology*
  • Myositis, Inclusion Body / pathology
  • Perforin
  • Pore Forming Cytotoxic Proteins / biosynthesis
  • T-Lymphocytes / pathology

Substances

  • CD8 Antigens
  • Complement Membrane Attack Complex
  • Cytokines
  • DYSF protein, human
  • Dysferlin
  • Membrane Glycoproteins
  • Membrane Proteins
  • Muscle Proteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Interferon-gamma
  • Granzymes