PRF1 and juvenile idiopathic arthritis: The importance of perforin is further highlighted by the fact that perforin mutations lead to FHL type 2 and are linked to the autoimmune lymphoproliferative syndrome, and juvenile rheumatoid arthritis and macrophage activation syndrome (Grom et al., 2003; Molleran Lee et al., 2004; Voskoboinik et al., 2004, 2005b; Ishii et al., 2005; Villanueva et al., 2005; Clementi et al., 2006; Bryceson et al., 2007; Chia et al., 2012).