Alloimmune neonatal neutropenia due to an antibody to the neutrophil Fc-
gamma receptor III with maternal deficiency of CD16 antigen
DF Stroncek, KM Skubitz, LB Plachta, RA Shankar, ME Clay, J Herman, HB Fleit and J McCullough
Department of Laboratory Medicine, University of Minnesota Medical School,
Minneapolis.
Antibodies to the neutrophil-specific antigens NA1 and NA2 are associated
with alloimmune neonatal neutropenia (ANN), autoimmune neutropenia of
childhood, and acute pulmonary transfusion reactions. These antigens have
been found to be located on the neutrophil Fc-gamma receptor III (FcRIII).
The mother of a child with ANN was found to lack both NA antigens and to
produce an antibody that reacted with all normal neutrophils tested. We
used maternal antibody and a CD16 monoclonal antibody (MoAb) that has
specificity for FcRIII to immunoblot and immunoprecipitate neutrophil
membranes of various NA phenotypes. Both antibodies immunoblotted an
approximately 40- to 70-Kd glycoprotein (GP) on NA1, NA2-positive membrane,
an approximately 40- to 55-Kd GP on NA1-homozygous membranes, and an
approximately 55- to 70- Kd GP on NA2-homozygous membranes. Both antibodies
also immunoprecipitated a 50- to 80-Kd GP from NA1, NA2-positive cells, a
50- to 60-Kd GP from NA1-homozygous cells, and a 55- to 80-Kd GP from NA2-
homozygous cells. To further examine the specificity of the maternal
antibody, sequential immunoprecipitation studies were performed using
maternal antisera and a CD16 MoAb. After extracts of 125I surface- labeled
neutrophils were precleared with maternal serum, CD16 MoAbs no longer
immunoprecipitated any GP. Neither the CD16 MoAb nor a rabbit polyclonal
antibody specific for FcRIII detected any GP in maternal neutrophil
membranes by immunoblotting. Neutrophil FcRIII is a glycosyl-
phosphatidylinositol anchored membrane GP as is decay accelerating factor
and both are absent from neutrophils of patients with paroxysmal nocturnal
hemoglobinuria (PNH). Maternal neutrophil membranes were probed with
antibody specific for DAF and an 80-Kd GP was detected. This woman also has
had no clinical evidence of PNH. These studies provide further evidence
that the NA1 and NA2 antigens are on FcRIII and identify a healthy person
whose neutrophils lack not only the neutrophil specific antigens NA1 and
NA2 but multiple other epitopes of FcRIII and, therefore, likely lack
FcRIII entirely.
Volume 77,
Issue 7,
pp. 1572-1580,
04/01/1991
Copyright © 1991 by The American Society of Hematology
