A total of 172 (53.8%) had causal associations with death directly and through the mediators hyperferritinemia and macrophage activation syndrome (MAS) and also had direct causal associations with increased C-reactive protein, ferritin, and interleukin 18 binding protein, which in turn had direct causal associations with decreased ADAMTS 13 activity and decreased whole blood ex vivo tumor necrosis factor response to endotoxin. This evidence concerns the gene IL18BP and macrophage activation syndrome.