In this regard, one of the most critical issues (from both a rheumatologic and immunological perspective) is represented by the actual contribution of the LN to the induction, maintenance, and perpetuation of the autoimmune response, with specific reference to the activation of ACPA-positive B lymphocytes, an RA-specific autoimmune trait related to a more severe course of the disease and contributing to the upstream phases of osteoclastogenesis [78, 79]. The gene discussed is PRTN3; the disease is rheumatoid arthritis.