Inflammatory myopathies

Why are inflamed muscles weak?

Idiopathic inflammatory myopathies (IIMs) are a group of muscle disorders caused by an immune-mediated attack on skeletal muscle tissue, and consist of polymyositis (PM), dermatomyositis (DM), inclusion body myositis IBM), non-specific inflammatory myopathy (NIM) and necrotising autoimmune myopathy (NAM). All these myopathies present with some level of weakness. The exact mechanism of weakness in IIMs is still unknown, but may theoretically be from a decrease in the actual number of muscle fibres, decreased contractility (performance) of the individual muscle fibres, or both. To date, it has been assumed this weakness result from a decrease in the number of muscle fibres as a result of necrosis. It is due to this assumption that the fibre contractility has been poorly studied. Only one study has looked at the muscle fibres’ function in untreated DM and IBM. However, this study had a number of flaws. Also, a number of observations argue against necrosis as the only factor contributing to the weakness. These include:

  • a lack of correlation between weakness and the degree of inflammation in muscle,
  • the relatively small amount of necrotic fibres on muscle histology as compared to the degree of weakness, and
  • how quickly patients respond to the treatment with corticosteroids.

Other non-immune effects on muscle may also contribute significantly to weakness in IIMs by affecting the contractile apparatus. These include an acquired deficiency of AMP-deaminase 1 (possibly interleukin-1 mediated) and depression of muscle fibre contractility by tumour necrosis factor α (TNF-α), as suggested by animal studies. Furthermore, the mechanism by which corticosteroids improve muscle function is also poorly studied. Possible explanations include the inhibition of secretion of TNF-α and decreased levels of TNF-α receptors, as well as increased AMP-deaminase 1 enzyme via decreased expression of interleukin-1.

What are we doing?

We are currently comparing the contractile properties of single muscle fibres from patients with untreated IIMs to those of healthy volunteers. Fortunately, we have also been able to obtain a muscle biopsy from patients after they have been treated with corticosteroids. Apart from the functional single fibre tests, we are also assessing a number of proteins (as mentioned above) in the muscle.

Collaborators

Franclo Henning (PhD candidate, University of Cape Town)

Jonathan Carr (Tygerberg hospital, University of Stellenbosch)