20S proteasome represents the proteolytic core complex for cytoplasmic protein degradation that is involved in the activation and regulation of the immune response. In this context, proteasome generates antigenic peptides for the MHC class I pathway and activates NF-κB. In a recent analysis, we could identify a frequent humoral autoimmune response directed against specific proteasomal subunits in patients with autoimmune myositis, systemic lupus erythematosus and primary Sjögren’s syndrome. The outer ring subunit HC9(α3) was identified as the predominant target of the anti-proteasome response in these entities. In addition to the reactivity against HC9(α3), patients with primary Sjögren’s syndrome expressed a more polyspecific recognition pattern of proteasomal subunits involving the active inner ring proteins. In follow-up analysis, anti-proteasome antibody titers revealed a correlation with disease activity in patients with autoimmune myositis and systemic lupus erythematosus. The current review summarizes recent data providing evidence that the 20S proteasome represents an important target of the humoral autoimmune response in systemic autoimmune diseases and extends insight into pathogenic aspects of these diseases.

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