DEFECTIVE NATURAL-KILLER-CELL FUNCTION IN PATIENTS WITH HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS AND IN FIRST DEGREE RELATIVES

Hemophagocytic lymphohistiocytosis (HLH), also referred to as familial erythrophagocytic lymphohistiocytosis, is a rare disorder of infancy associated with proliferation of activated histiocytes and T cells, an emia, thrombocytopenia, and fevers. This disorder appears to be due to the uncontrolled activation of T cells producing IL-2, tumor necrosis factor-alpha, and interferon-gamma. Untreated, the disorder is univer sally fatal. Various deficits in immune function have been described d uring acute disease activity including impaired T cell function, impai red monocyte-mediated antibody-dependent cytotoxicity, impaired natura l killer cell function, and impaired IL-1 production. We examined natu ral killer cell function in familial HLH patients to determine whether this finding was consistently associated with the disease. We also ex amined natural killer cell function in asymptomatic parents and siblin gs of patients. Impaired natural killer cell function was identified i n all patients and in some family members, including obligate carrier parents. This implies that one potential genetic defect in HLH may res ult in depressed natural killer function, but that this may not be suf ficient to reliably predict eventual progression to disease.