This includes apparent differences in the immune threshold of disease initiation: While almost all patients with perforin null mutations present with disease in the first 6 months of life often without apparent infectious trigger [13], PKO mice held under SPF conditions remain healthy and develop HLH only after persistent infection with perforin‐controlled LCMV or MCMV, but not when infected with various other viruses, that are eliminated in the absence of perforin [11, 16, 21]. Here, PRF1 is linked to hemophagocytic syndrome.