Two cases of maternal alloimmunization against human neutrophil alloantigen-4b, one causing severe alloimmune neonatal neutropenia.
BACKGROUND
Human neutrophil antigen (HNA)-4a/4bw is encoded by 230G>A in ITGAM, which results in an Arg61His substitution of the αM chain (CD11b) of complement receptor 3 (CR3; CD11b/18 or Mac-1). HNA-4a antibodies have been detected in the sera of female blood donors and in maternal sera that caused alloimmune neonatal neutropenia (ANN), in which maternal immunoglobulin (Ig)G antibodies against a paternally inherited HNA cross the placenta and destroy fetal and neonatal neutrophils. However, to date, antibodies specific for HNA-4b have not been reported. Here, we report the first two examples of HNA-4b antibodies.


METHODS
The two sera studied were both from previously pregnant females, one a multiparous female blood donor implicated in two separate transfusion reactions and the second a mother whose first pregnancy resulted in the birth of a severely neutropenic (0 × 10(6) neutrophils/L) infant affected with ANN. Serum neutrophil antibody testing was by flow cytometry and CD11b/18 monoclonal antibody immobilization of granulocyte antigens assay, and HNA genotyping was performed by polymerase chain reaction with sequence-specific priming and allele-specific 5' exonuclease assays.


RESULTS
Sera from both women contained IgG antibodies reactive only with HNA-4b+ neutrophils and both typed HNA-4a/a. Both were immunized through pregnancy since their husbands and children all typed HNA-4a/b.


CONCLUSIONS
The serologic results, together with the genotype results, confirm that these are the first reported cases of neutrophil antibodies specific for HNA-4b.
Platelet & Neutrophil Immunology Laboratory, BloodCenter of Wisconsin, Milwaukee, Wisconsin.|Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin.
Brian R
BR
Curtis
NYU Langone Medical Center, New York, New York.
Ashley S
AS
Roman
Platelet & Neutrophil Immunology Laboratory, BloodCenter of Wisconsin, Milwaukee, Wisconsin.
Mia J
MJ
Sullivan
Michigan Blood, Grand Rapids, Michigan.
Cindy S
CS
Raven
Michigan Blood, Grand Rapids, Michigan.
Judy
J
Larison
Michigan Blood, Grand Rapids, Michigan.
Lee Ann
LA
Weitekamp
D016824:Antigens, Human Platelet / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D005260:Female; D054502:Histocompatibility, Maternal-Fetal / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D009503:Neutropenia / Q000175:diagnosis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011247:Pregnancy
C510800:4b alloantigen, human; D016824:Antigens, Human Platelet; D015415:Biomarkers; C000620863:HNA-4b antigen, human; D007518:Isoantibodies; D007519:Isoantigens