Humoral-cellular cross-talk closes the loop: complement activation (C3a) and neutrophil extracellular traps (CitH3, NE) connect coagulation, innate immunity, and tissue injury, marking the transition from acute SIRS to chronic PIICS, persistent inflammation, immunosuppression and catabolism syndrome [9,10,11]. The gene discussed is C3; the disease is systemic inflammatory response syndrome.