PRF1 and systemic-onset juvenile idiopathic arthritis: Recent studies have shown that dysfunction of natural killer (NK) cells due to mutations of the genes for perforin and Munc 13-4 leads to familial lymphohistiocytosis, whereas it has been suggested that decreased NK cell activity and abnormal levels of perforin are involved in the macrophage activation syndrome of systemic-onset juvenile rheumatoid arthritis [20].