**4.3 Conclusions**

As previously described in other autoimmune diseases, a role for B-cells in IM is implied by the clinical improvement in patients administered Rituximab® therapy, including improvements in muscle strength. Some patients relapsed as their B-cell pools repopulated and depletion of autoantibody titres was variable (Chung, Genovese, & Fiorentino, 2007; Cooper et al., 2007; Levine, 2005). The potential of B-cells as therapeutic targets is further supported by the elevations in serum levels and gene expression of B-cell activating factor (BAFF) in IM patients, a cytokine crucial for B-cell maturation and survival, which is also thought to play a role in autoantibody production (Krystufkova *et al.*, 2008; Salajegheh *et al.*, 2010).

Despite all the evidence described here implicating B-cells and loss of B-cell tolerance in the IM, numerous questions still remain to be resolved, including identification of the stimulating antigens and epitopes, sequence characteristics and pathogenicity of highaffinity, antigen-specific antibodies produced *in situ*, and the factors regulating and controlling these autoimmune reactions. The resolution of these questions will enhance our understanding of the immune pathology of IM and facilitate the diagnosis, treatment and management of these diseases.
