Prenatal typing of Rh and kell blood group system antigens: The edge of a watershed

Ellen van der Schoot, C.; Martine Tax, G.H.; Rijnders, Robbert J.P.; de Haas, Masja; Christiaens, Godelieve C.M.L.

doi:10.1053/tmrv.2003.50001

« Previous Next »Transfusion Medicine Reviews
Volume 17, Issue 1 , Pages 31-44, January 2003

Prenatal typing of Rh and kell blood group system antigens: The edge of a watershed

C. Ellen van der Schoot
- Department of Experimental Immunohematology, Sanquin Division, CLB, Academic Medical Center, University of Amsterdam Amsterdam, The Netherlands
- Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherland
- Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
- Division of Obstetrics, Neonatology and Gynecology, University Medical Center Utrecht, The Netherlands
- Address reprint requests to C. Ellen van der Schoot, MD, PhD, Department of Experimental Immunohematology, Sanquin, Division CLB, Plesmanlaan 10, 1066 CX Amsterdam, The Netherlands.
G.H. Martine Tax
- Department of Experimental Immunohematology, Sanquin Division, CLB, Academic Medical Center, University of Amsterdam Amsterdam, The Netherlands
- Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherland
- Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
- Division of Obstetrics, Neonatology and Gynecology, University Medical Center Utrecht, The Netherlands
Robbert J.P. Rijnders
- Department of Experimental Immunohematology, Sanquin Division, CLB, Academic Medical Center, University of Amsterdam Amsterdam, The Netherlands
- Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherland
- Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
- Division of Obstetrics, Neonatology and Gynecology, University Medical Center Utrecht, The Netherlands
Masja de Haas
- Department of Experimental Immunohematology, Sanquin Division, CLB, Academic Medical Center, University of Amsterdam Amsterdam, The Netherlands
- Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherland
- Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
- Division of Obstetrics, Neonatology and Gynecology, University Medical Center Utrecht, The Netherlands
Godelieve C.M.L. Christiaens
- Department of Experimental Immunohematology, Sanquin Division, CLB, Academic Medical Center, University of Amsterdam Amsterdam, The Netherlands
- Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherland
- Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
- Division of Obstetrics, Neonatology and Gynecology, University Medical Center Utrecht, The Netherlands

Knowledge of the molecular basis of the blood group systems has enabled the development of assays for blood group genotyping. At this time, polymerase chain reaction (PCR)-based assays validated on fetal meterial obtained by invasive means (chorionic villus sampling or amniocentesis) are available for all clinically relevant fetal blood groups, However, only Rh typing (D, C, c, E, and e) and K1 genotyping assays are discussed in this review. Importantly, one must remember that results of genotyping assays will not always be concordant with serological typing. Thus, the RhD genotyping assays have to be modified in response to increased understanding of the molecular biology of this blood group system. RhD typing assays should produce negative results when tested on the black RhD-negative RHD alleles, RHDψ and r's. PCR-based assays can be used to determine paternal zygosity. For RhD zygosity testing, the real-time quantitative PCR approath and the direct detection of the hybrid Rhesus box, which is the result of the deletion of the RHD gene are available. Recently, methods for noninvasive prenatal genotyping have been investigated. The use of fetal cells circulating in the meternal circulation has been explored; however, the scarcity of circulating fetal cells has limited the use of this approach. More promising are the results obtained with RhD typing assays with cell-free fetal DNA, which is present in the maternal circulation in a concentration of 25 genomic equivalents per milliter of maternal blood in early pregnancy increasing to 100 copies per milliliter in the third trimester, which is cleared from the circulation within a few hours of delivery. The positive predictive value of this approach is virtually 100%, but false-negative results are (infrequently) encountered. Therefore, this assay can at present only be used for screening of RhD-negative women to make the use of antenatal prophylaxis more targeted and hence more cost-effective. For the clinical managment of the pregnancies of alloimmunized women, the development of a control for the presence and the amplification of fetal DNA is needed, which is at present only available in male pregnancies. Assays for the genotyping of the other Rh antigens or Kell antigens with cell-free fetal DNA have not yet been described.

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