Neonatal alloimmune neutropenia attributed to maternal immunoglobulin G antibodies against the neutrophil alloantigen HNA-1c (SH): a report of five cases

BACKGROUND: Neonatal alloimmune neutropenia (NAN) occurs when maternal immunoglobulin G (IgG) antibodies enter fetal circulation and destroy neonatal neutrophils. Whether antibodies specific for the neutrophil antigen HNA-1c (SH) can cause NAN is uncertain, because in three of four reported cases, other neutrophil-specific antibodies were present. In this report, we describe five cases of NAN, in which only anti-HNA-1c was detected in maternal serum. STUDY DESIGN AND METHODS: HNA-1c antibodies were detected with flow cytometry immunofluorescence (FCI) and the monoclonal antibody (MoAb) immobilization of granulocyte antigens (MAIGA) assay. Genotyping for HNA-1c was performed by allele-specific polymerase chain reaction amplification of DNA. RESULTS: All five maternal serum samples contained IgG antibodies with specificity for HNA-1c detected in both FCI and MAIGA assay. Of CD16-specific MoAbs evaluated, only MBC238.7 was optimal for detection of antibody by MAIGA assay. Recombinant human granulocyte-colony-stimulating factor (rHuG-CSF) was effective in raising neutrophil counts in the two infants treated in this manner. CONCLUSION: Severe NAN can be caused by maternal antibodies specific for HNA-1c (SH) alone. Use of an appropriate MoAb is critical for detection of anti-HNA-1c by MAIGA assay. rHuG-CSF is an effective therapy in infants with NAN caused by anti-HNA-1c.