Fig. 5.

A possible scenario for the pathogenesis of sIBM is that it may start with inflammation within muscle (the different actors are represented in red). The rush of leukocytes attracted by chemokines and cytokines may induce fibre injury and HLA-I overexpression. If the protein degradation systems are overloaded (due to genetic predisposition, particular HLA-I subtypes or ageing), amyloid and other protein deposits (represented in green) may appear within muscle fibres, reinforcing the myopathy in a vicious circle. The opposite scenario where amyloid deposits come first leading to a secondary inflammatory reaction is less probable since (apart some rare exceptions) neither hereditary inclusion body myopathy nor animal models of forced amyloid deposits (with proteasomal and/or autophagosomal pathway deficiencies) are accompanied by inflammation