PRTN3 and rheumatoid arthritis: Specifically, in the pre-disease stage of RA, the breach of immune tolerance to citrullinated antigens appear to be triggered in genetically predisposed individuals by protein citrullination at putative extra-articular sites, such as the periodontal tissue during Porhyromonas gingivalis-induced periodontitis or in the lung of smokers (13–15), which gives rise to a restricted ACPA repertoire.