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Two cases of maternal alloimmunization against human neutrophil alloantigen‐4b, one causing severe alloimmune neonatal neutropenia
Author(s) -
Curtis Brian R.,
Roman Ashley S.,
Sullivan Mia J.,
Raven Cindy S.,
Larison Judy,
Weitekamp Lee Ann
Publication year - 2016
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.13287
Subject(s) - neonatal alloimmune thrombocytopenia , antibody , immunology , neutropenia , medicine , antibody opsonization , antigen , pregnancy , isoantibodies , genotype , biology , opsonin , fetus , gene , genetics , toxicity , biochemistry
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. STUDY DESIGN AND 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.