Distribution of fetal and embryonic hemoglobins in fetal erythroblasts enriched from maternal blood.
OBJECTIVE
To determine the distribution of embryonic and fetal hemoglobin chains in fetal erythroblasts isolated from maternal blood in the first trimester of pregnancy and establish the feasibility of using these chains as markers for fetal cell identification.


METHODS
Maternal blood was obtained from 187 singleton pregnancies at 11-14 weeks of gestation immediately before fetal karyotyping by chorionic villus sampling. In all cases included in this study the fetal karyotype was normal. Fetal erythroblasts were isolated using triple density gradient separation and anti-CD71 magnetic cell sorting techniques. The enriched erythroblasts were stained with Kleihauer-Giemsa and with fluorescent antibodies for the zeta (z), epsilon (e) and gamma (g) globin chains. The percentage of fetal cells positive for each stain was calculated. Fluorescent in situ hybridization (FISH) for X and Y chromosomes was also performed. Comparison was made with the percentage of cells with positive Y-signal FISH in pregnancies with male fetuses.


RESULTS
The percentage of fetal erythroblasts stained positive was 37% for the z and 95% for both e and g globin chains, as well as the Kleihauer-Giemsa staining. There was a significant association between the Kleihauer-Giemsa stained cells and those stained with e and g globin chains. There was also an association between cells with Y-signals and those stained with e and g globin chains.


CONCLUSIONS
Embryonic hemoglobin chains can be detected in the enriched fetal erythroblasts, with higher percentages of the e rather than the z globin chains. These chains are therefore potentially unique markers to be used in the identification of cells of fetal origin from maternal blood for prenatal diagnosis of genetic and chromosomal abnormalities.
Al-Mufti
R
R
Harris Birthright Research Center For Fetal Medicine, Department of Hematologic Medicine, Department of Molecular Medicine, King's College Trust School of Medicine, London, England.
Hambley
H
H
Farzaneh
F
F
Nicolaides
K H
KH
D015415:Biomarkers / Q000097:blood; D002469:Cell Separation; D020732:Cytogenetic Analysis; D004622:Embryo, Mammalian / Q000737:chemistry*; D004900:Erythroblasts / Q000737:chemistry*; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis*; D005333:Fetus / Q000737:chemistry; D005914:Globins / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D008431:Maternal-Fetal Exchange; D011247:Pregnancy
D015415:Biomarkers; D006454:Hemoglobins; D005914:Globins; D005319:Fetal Hemoglobin