CHARACTERISTIC IMMUNE ABNORMALITIES IN HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatenin g syndrome characterized by fever, hepatosplenomegaly, pancytopenia, a nd infiltration of vital organs by non-langerhans histiocytes and is r apidly fatal without early diagnosis and institution of therapy. Immun e dysregulation is thought to be responsible for the disease. Patients and Methods: Extensive immune evaluation was performed on 13 consecut ive patients diagnosed with HLH over a 4-year period to characterize e xisting immunologic abnormalities in order to improve early diagnosis. Evaluation included quantitative immunoglobulins, immunophenotyping, mitogen-induced lymphoproliferation, natural killer (NK) cell function , and cytotoxic T cell lymphocytolysis (CTL).Results: Immunoglobulin l evels showed no consistent abnormality. Immunophenotyping showed an ab solute decrease in number of B cells but normal numbers and proportion al distribution of T cell subsets and NK cells. Most patients demonstr ated decreased proliferative responses to mitogens (10/13) and severel y decreased to absent T cell cytotoxicity (11/12) and NK cytotoxic fun ction (13/13). Conclusions: Our results show that while humoral immuni ty is essentially intact, cellular immune function is significantly im paired in the vast majority of patients with HLH. The coincident findi ng of profoundly decreased T cell cytotoxicity along with absent NK cy totoxicity suggests that patients with active HLH may have global cyto toxic dysfunction. Since the majority of our patients were studied pri or to starting therapy, we feel that these findings reflect the pathop hysiologic process and are not therapy related. Unclear from the prese nt work is whether these findings represent primary or secondary dysfu nction. We conclude from these studies that profoundly decreased CTL f unction and absence of NK cell function are characteristic immunologic features of HLH and may serve as additional laboratory data, in conju nction with currently proposed diagnostic guidelines, to support a dia gnosis of HLH.