Non-invasive determination of the paternal HLA haplotype of a fetus using kinetic PCR to detect fetal microchimerism in maternal plasma.
Knowledge of fetal HLA type can be important if cord blood (CB) is being considered as a stem cell source for transplantation. The feasibility of determining the paternally inherited HLA haplotype of a fetus was explored through analysis of fetal DNA in the maternal circulation. A 5-year-old child with relapsed acute leukemia was a candidate for transplantation. The HLA type of the fetal sibling was needed to assist with evaluation of this potential cord blood donor. DNA was isolated from maternal plasma and whole blood. Kinetic PCR using sequence-specific primers for paternal HLA-A, -B, and -DRB1 alleles was performed. Alleles corresponding to one paternal haplotype were detectable in plasma, but not in whole blood. Alleles from the alternative haplotype were not detectable. This demonstrated that the fetus shared at least one haplotype with the patient and therefore arrangements were made to bank the CB. The maternal haplotype of the fetus could not be determined in the presence of maternal DNA. The prenatal fetal typing was confirmed by typing the newborn's CB. This rapid non-invasive technique may facilitate the selection of CB units for banking based on needed HLA types.
Reed
W
W
Blood Centers of the Pacific, Irwin Center, Scientific Services Division, San Francisco, CA, USA.
Kong
D Z
DZ
Lee
T-H
TH
Cowan
M J
MJ
Busch
M P
MP
Baxter-Lowe
L A
LA
D000208:Acute Disease; D002675:Child, Preschool; D002678:Chimera / Q000097:blood* / Q000196:embryology* / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D005220:Fathers; D005260:Female; D005333:Fetus / Q000502:physiology*; D006680:HLA Antigens / Q000097:blood* / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics* / Q000502:physiology*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D007938:Leukemia / Q000601:surgery; D008297:Male; D009035:Mothers; D016133:Polymerase Chain Reaction / Q000379:methods*; D011247:Pregnancy; D012008:Recurrence; D014184:Transplantation, Homologous / Q000379:methods
D006680:HLA Antigens; D004247:DNA