Role of DOCK8 in Cytokine Storm Syndromes

Cytokine storm syndromes (CSS), including hemophagocytic lymphohistiocytosis (HLH), are increasingly recognized as hyperinflammatory states leading to multi-organ failure and death. Familial HLH (FHL) in infancy results from homozygous genetic defects in perforin-mediated cytolysis by CD8 T-lymphocytes and natural killer (NK) cells. Later onset CSS are frequently associated with heterozygous defects in FHL genes, but genetic etiologies for most are unknown. We identified rare DOCK8 variants in CSS patients.