Abstract

Idiopathic inflammatory myopathies (IM) constitute a heterogeneous group of chronic disorders which include dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). These diseases represent distinct pathological entities but, most often, share predominant inflammation in muscle tissue. Many of the immunopathogenic processes behind the IM remain poorly understood until today, however, the role played by various inflammatory mediators becomes more and more clear. Induction of major histocompatibility complexes on the membranes, makes that IM muscle fibers actively participate to the immune processes by becoming antigen presenters. Several myositis-specific autoantibodies have been recognized, typing different subgroups of patients with distinct clinical phenotype. Cytokines, the master regulators of leukocyte activation and migration, have especially been recognized as crucial factors. The IM are characterized by strong expression of subsets of Tumor Necrosis Factors (TNFα, LTβ, BAFF), Interferons (IFNα/β/γ), Interleukins (IL-1/6/12/15/18/23) and Chemokines (CXCL9/10/11/13, CCL2/3/4/8/19/21) in the muscle tissue. The latter are important for attracting distinct subsets of T-cells, B-cells, macrophages and dendritic cells, and for their intra-muscular organization. The complex inflammatory network in IM pinpoints targets for neutralization through a selective therapeutic approach as a necessary alternative for patients that do not respond to conventional immune-suppressants. Results so far are promising, but have also shown the necessity for further subtyping of patients to develop future precision therapies and predict treatment outcome.