PRF1 and infection: pHLH is caused by genetic mutations associated with immune dysfunction, such as LYST, SH2D1A, and PRF1, while sHLH is triggered by significant immune system insults, such as infections (e.g., EBV), malignancies, or autoimmune diseases ​[11]. The main clinical manifestations of HLH include fever, hepatosplenomegaly, lymphadenopathy, cytopenias, hyperferritinemia, hypertriglyceridemia, and/or hypofibrinogenemia ​[12].