Table 1 Potential target for novel therapeutical approaches for patients with IIM (modified from [19])
From: Drugs in induction and treatment of idiopathic inflammatory myopathies
| Â | Target | Relevance for IIM | Actual data |
|---|---|---|---|
B cells | CD20+ B cells | B cells and CD138+ plasma cells are found in muscle tissue. B cells producing autoantibodies and cytokines can also act as antigen presenting cells | Some studies [20–22] and a RCT [23] report an improvement after rituximab (chimeric antiCD20 monoclonal antibody) treatment in muscle performance, CK levels, antibody levels and stabilization of ILD |
T cells | CD28null T cells | Persistence in peripheral blood and muscle infiltrates even after prednisone treatment. CD28null are cytotoxic in close proximity to muscle | No data available. However, alemtuzumab (targeted antiCD52, present on CD28null T cells) seems to be efficacy in IBM patients [15] |
T cells costimulations | CD28 is constitutively present on T cells and interaction with CD80 causes T cells activation | Abatacept (a fusion protein of the Fc region of the IgG1 fused to the extracellular domain of CTLA-4) seems to be effective in IIM patients in case reports and case series [26] | |
Citokines | TNF-α | TNF-α can have a direct impact on muscle function, although its importance in PM and DM is not well defined | Controversial effects of anti-TNF; infliximab may worsen refractory cases [27] |
IL-1 | IL-1 α and β are consistently expressed in muscle tissue of PM and DM. IL-1 induces transmigration of immune cells to the site of inflammation | Case reports and case series showed a clinical response to IL-1 blockade with anakinra (IL-1 receptor antagonist) [28] | |
IL-6 | IL-6 is expressed in muscle tissue in some PM and DM patients. It supports the growth of B cells, is an antagonist to regulatory T cells promoting the cytotoxic T cells | Two case reports on the successful treatment of PM with tocilizumab (humanized anti-IL-6 receptor antibody). Efficacy in experimental animal model of myositis [29] | |
IFN type I | IFNs up-regulate MHC class I and class II and control function and regulation of T cells. Anti Jo-1-positive sera induced IFN-a production | Monoclonal antibodies targeting IFN-α and IFN-γ are being investigated in connective tissue diseases. Sifalimumab (anti-IFN α monoclonal antibody) was well tolerated in a phase I clinical trial of patients with PM and DM [30] |