CTSS and rheumatoid arthritis: Cathepsin S has an essential role in major histocompatibility complex (MHC)–II–mediated antigen presentation [15], autoantibody production [16] and extracellular matrix degradation [17], and has been previously reported to control experimental RA development in mouse [18], as well as to be increased in both the synovial fluid [19] and the systemic circulation of patients with RA [20].