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.


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.


CONCLUSIONS
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.
Curtis
Brian R
BR
Platelet & Neutrophil Immunology Laboratory, The Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin 53233, USA. brcurtis@bcsew.edu
Reno
Corey
C
Aster
Richard H
RH
D000328:Adult; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood; D007519:Isoantigens / Q000276:immunology*; D009503:Neutropenia / Q000188:drug therapy / Q000209:etiology*; D009504:Neutrophils / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D017452:Receptors, IgG / Q000032:analysis; D011994:Recombinant Proteins
D007074:Immunoglobulin G; D007518:Isoantibodies; D007519:Isoantigens; D017452:Receptors, IgG; D011994:Recombinant Proteins; C067704:neutrophil-specific antigen NA1, human; D016179:Granulocyte Colony-Stimulating Factor