Ultrastructural localization of glycoprotein IIIa (GPIIIa, beta 3 integrin) on placental syncytiotrophoblast microvilli: implications for platelet alloimmunization during pregnancy.
BACKGROUND
Fetal and neonatal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-1a more commonly occurs in first pregnancies, unlike hemolytic disease of the newborn. Anti-D is produced after D+ fetomaternal hemorrhage; this usually occurs at parturition. Anti-HPA-1a could develop during pregnancy if maternal immunization is stimulated by HPA-1a expressed not only on platelets but also on other fetal cells.


METHODS
An ultrastructural study of fetal placental chorionic villi was undertaken to determine the localization of glycoprotein (GP)IIIa carrying the HPA-1a/1b polymorphism. First trimester and term villi were incubated with a monoclonal antibody (MoAb) to GPIIIa or with positive control MoAbs (anti-placental alkaline phosphatase and ED822 MoAb) to villous syncytiotrophoblast (ST). Binding of MoAbs was detected with a gold-conjugated secondary antibody before processing the tissues and examination of ultrathin sections in an electron microscope.


RESULTS
Gold particles were evident on microvilli on the apical surface of ST when labeled with anti-GPIIIa and the placenta-specific MoAbs but not with an isotype control antibody. Immunolabeling for anti-GPIIIa on first trimester ST was similar to that of term ST.


CONCLUSIONS
The apical surface of the ST is bathed in maternal blood. During the natural regenerative process of human placenta, senescent parts of the ST are shed into maternal blood during pregnancy. This includes both apoptotic ST nuclei and microparticulate ST debris. The presence of GPIIIa on this circulating ST cellular material could be the source of HPA-1a alloantigen causing primary immunization of susceptible primigravidae early enough for anti-HPA-1a to cause fetal thrombocytopenia during a first pregnancy.
Kumpel
Belinda M
BM
Bristol Institute for Transfusion Sciences, National Blood Service, Bristol, UK. belinda.kumpel@nbs.nhs.uk
Sibley
Karin
K
Jackson
David J
DJ
White
Graham
G
Soothill
Peter W
PW
D000911:Antibodies, Monoclonal / Q000276:immunology; D016824:Antigens, Human Platelet / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology*; D002824:Chorionic Villi / Q000276:immunology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007223:Infant; D039661:Integrin beta3 / Q000276:immunology* / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology*; D016253:Microscopy, Immunoelectron; D008871:Microvilli / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000276:immunology; D011261:Pregnancy Trimester, First; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000097:blood / Q000276:immunology*; D014327:Trophoblasts / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007518:Isoantibodies