HISTIOCYTES IN FAMILIAL AND INFECTION-INDUCED IDIOPATHIC HEMOPHAGOCYTIC SYNDROMES MAY EXHIBIT PHENOTYPIC DIFFERENCES

Familial hemophagocytic syndrome (FHS) and infection-associated hemophagocytic syndrome (IAHS) usually present with fever, pancytopenia, hepatosplenomegaly, signs of hepatic dysfunction, bleeding diathesis, and neurological manifestations. FHS is almost uniformly fatal, and IAHS is associated with high mortality. The only distinguishing characteristics are lack of family history and association with infection in the latter. Despite this, sporadic cases of FHS and culture-negative examples of IAHS (idiopathic HS) can be difficult to distinguish and the distinction may have important implications for treatment and family planning. We evaluated the immunophenotype of the macrophages (M-phi-s) in frozen tissue sections from three cases of hemophagocytic syndrome using a very large panel of monocyte/M-phi-associated monoclonal antibodies and an immunoperoxidase technique. The clinical and laboratory features suggested that two were examples of FHS (one with strong family history) and that the third was IAHS/ idiopathic HS. The results supported the clinical impressions by showing that the antigenic phenotypes of the FHS cases were nearly identical and different from that of the case of presumed IAHS/ idiopathic HS. Specifically, M-phi-s from the FHS cases expressed complement receptors, 1, 2, and 3 (CD35, CD21, and CD11b, respectively), the monocyte antigen CD36, and the "activation" antigens CD25 (IL2-R) and CD30 (Ki-1), while those from the IAHS/idiopathic case did not. These studies also demonstrated that the M-phi-s in these cases exhibited some phenotypic differences from those in control tissues, that is, expression of the pan-M-phi antigen CD14, the M-phi subset antigen identified by antibody G16/1, complement receptors, certain monocyte antigens, and M-phi "activation " antigens. Furthermore, S-100 protein, not typically found in mononuclear phagocytes, was detected in the hemophagocytic M-phi-s from these cases. These results, which need to be confirmed by analysis of a larger number of cases, suggest that FHS can be distinguished from IAHS/ idiopathic HS by phenotypic analysis and, further, that the M-phi-s in these disorders are phenotypically different from those in normal tissues.