Neonatal neutropenia and bacterial sepsis associated with placental transfer of maternal neutrophil-specific autoantibodies

BACKGROUND: Passively acquired neonatal neutropenia is an infrequently reported complication of maternal autoimmune neutropenia (AIN). Two affected siblings are described. The firstborn developed Citrobacter meningitis and was permanently disabled. The second was successfully managed with pre- and postnatal injections of recombinant human granulocyte colony-stimulating factor (rHuG-CSF). STUDY DESIGN AND METHODS: Neutrophil-specific antibodies were evaluated by flow cytometry (FC), monoclonal antibody immobilization of granulocyte antigens, and granulocyte agglutination assays. RESULTS: A neutrophil-reactive antibody was detected by FC in samples of the mother's serum spanning a 4-year time frame. This antibody reacted with neutrophils from the mother, father, and their first infant and with 18 of 20 target neutrophils tested. In serologic studies, it was shown that the antibody was not specific for the commonly recognized neutrophil-specific alloantigens HNA-1a (NA1), HNA-1b (NA2), HNA-1c (SH), HNA-2a (NB1), or HNA-3a (5b). CONCLUSION: Severe neonatal neutropenia in the two siblings appears to have been caused by placental transfer of a maternal neutrophil-reactive autoantibody of undetermined specificity. Neutrophil counts should be evaluated in infants born to mothers with chronic neutropenia of possible autoimmune origin so that neutropenic infants can be carefully monitored and antibiotics and/or rHuG-CSF administered if indicated.