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Non-invasive determination of the paternal HLA haplotype of a fetus using kinetic PCR to detect fetal microchimerism in maternal plasma

Bone Marrow Transplantation volume 29, pages 527–529 (2002)Cite this article

Abstract

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.

Bone Marrow Transplantation (2002) 29, 527–529. doi:10.1038/sj.bmt.1703411

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References

  1. van den Berg H, Verjaal M, Boer K, Lardy NM . Prenatal HLA-matching to determine suitability for allogeneic bone marrow transplantation Bone Marrow Transplant 2000 25: 579 581

    Article  CAS  Google Scholar 

  2. Bianchi DW, Crombleholme TM, D'Alton ME . Fetology McGraw Hill: New York 2000

    Google Scholar 

  3. Lo Y, Hjelm N, Fidler C et al. Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma New Engl J Med 1998 339: 1734 1738

    Article  CAS  Google Scholar 

  4. Lo YM . Fetal DNA in maternal plasma: biology and diagnostic applications Clin Chem 2000 46: 1903 1906

    CAS  PubMed  Google Scholar 

  5. Lee TH, Paglieroni T, Ohto H et al. Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients Blood 1999 93: 3127 3139

    CAS  PubMed  Google Scholar 

  6. Reed WF, Lee TL, Trachtenberg E et al. Detection of microchimerism by PCR is a function of amplification strategy Transfusion 2001 41: 39 44

    Article  CAS  Google Scholar 

  7. Bianchi D, Zickwolf G, Weil G et al. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum Proc Natl Acad Sci USA 1996 93: 705 708

    Article  CAS  Google Scholar 

  8. Ariga H, Ohto H, Busch MP et al. Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for non-invasive prenatal diagnosis Transfusion 2001 41: 1524 1530

    Article  CAS  Google Scholar 

  9. Lo YM, Corbetta N, Chamberlain PF et al. Presence of fetal DNA in maternal plasma and serum Lancet 1997 350: 485 487

    Article  CAS  Google Scholar 

  10. Lo YM, Zhang J, Leung TN et al. Rapid clearance of fetal DNA from maternal plasma Am J Hum Genet 1999 64: 218 224

    Article  CAS  Google Scholar 

  11. Reed WF, Walters M, Trachtenberg E et al. Sibling donor cord blood banking for children with sickle cell disease Ped Path Mol Med 2001 20: 167 174

    Article  CAS  Google Scholar 

  12. Reed W, Walters M, Lubin BH . Collection of sibling donor cord blood for children with thalassemia J Pediatr Hematol Oncol 2000 22: 602 604

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This project was supported in part by University of California San Francisco fund No. 64297–406195, the National Institutes of Health through the NHLBI Special Center of Research grant in Transfusion Medicine (P50-HL-54476), the Pediatric Clinical Research Center Grant (M-O1-RRO1271–16), and a consortium with University of Louisville (RO1 HL64978). The authors thank Dr Kimie Fukuyama (University of California San Francisco) for critical reading of the manuscript. We thank our colleagues Keith Fichter, Tracey Mabardy and Jamie Paul for HLA sequencing.

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Authors and Affiliations

  1. Scientific Services Division, Blood Centers of the Pacific, Irwin Center, San Francisco, CA, USA

    W Reed, T-H Lee & MP Busch

  2. Department of Surgery, Immunogenetics and Transplantation Laboratory, University of California San Francisco, San Francisco, CA, USA

    DZ Kong & LA Baxter-Lowe

  3. Bone Marrow Transplantation Division, Department of Pediatrics, University of California, San Francisco, CA, USA

    MJ Cowan

  4. Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA

    MP Busch

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  1. W Reed
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  2. DZ Kong
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  3. T-H Lee
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  4. MJ Cowan
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  5. MP Busch
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  6. LA Baxter-Lowe
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Reed, W., Kong, D., Lee, TH. et al. Non-invasive determination of the paternal HLA haplotype of a fetus using kinetic PCR to detect fetal microchimerism in maternal plasma. Bone Marrow Transplant 29, 527–529 (2002). https://doi.org/10.1038/sj.bmt.1703411

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