IFNG and macrophage activation syndrome: The explanation for the relentless progression with HPS and MAS is that the antigen-presenting cell (APC)-cytotoxic cell synapse through TCR–MHC class I interaction results in activation of the CTL and production of IL-12, IL-18, IL-15, and IL-2, resulting in lymphoproliferation and IFNγ generation (19, 20).