Foetal Microchimerism Correlates With Foetal‐Maternal Histocompatibility Both During Pregnancy and Postpartum

HLA, vol. 104, pp. e15717

Abstract

Foetal cells are detectable in women decades postpartum, a state termed foetal microchimerism. The interplay between these semi-allogeneic foetal cells and the mother could be affected by genetic mismatches in the HLA loci. Here, we relate HLA allele and molecular mismatch values to the presence and quantity of foetal microchimerism in the maternal circulation during pregnancy and postpartum. A total of 76 pregnant women were included, of which 59 were followed up 1-8 years postpartum. Maternal and foetal DNA was genotyped for HLA class I and II loci. Foetal cells in maternal buffy coat were detected by qPCR, targeting inherited paternal alleles. Antibody-verified eplet mismatch and Predicted Indirectly Recognisable HLA Epitopes (PIRCHE) scores were calculated to quantify foetal-maternal histocompatibility from the mother's perspective. Circulating foetal cells were detected in 50.0% (38/76) of women during pregnancy, and 25.4% (15/59) postpartum. During pregnancy, HLA class II antibody-verified eplet mismatch load and PIRCHE scores correlated negatively with the presence and quantity of foetal cells in the maternal circulation. Postpartum, HLA class I allele mismatches correlated negatively with foetal microchimerism presence, while HLA class II allele mismatches, HLA class I and II antibody-verified eplet mismatch load, and PIRCHE-I and PIRCHE-II scores correlated negatively with both microchimerism presence and quantity. The correlation between mismatch parameters aimed at evaluating the risk of humoral and T cell-mediated allorecognition and foetal microchimerism was more evident postpartum than during pregnancy. The observed predictive effect of foetal-maternal histocompatibility on foetal microchimerism suggests that circulating foetal cells are subject to clearance by the maternal immune system. We propose that allorecognition of foetal cells in the maternal circulation and tissues influences any long-term effect that foetal microchimerism may have on maternal health.

Authors 12

1. Anne Cathrine Staff

   Oslo University Hospital · University of Oslo

   Affiliation as printed

   Division of Obstetrics and Gynaecology Oslo University Hospital Oslo Norway

   Institute for Clinical Medicine, Faculty of Medicine University of Oslo Oslo Norway

2. Heidi E. Fjeldstad

   Oslo University Hospital · University of Oslo

   Affiliation as printed

   Division of Obstetrics and Gynaecology Oslo University Hospital Oslo Norway

   Institute for Clinical Medicine, Faculty of Medicine University of Oslo Oslo Norway

3. Maria Belland Olsen

   Oslo University Hospital · University of Oslo

   Affiliation as printed

   Institute for Clinical Medicine, Faculty of Medicine University of Oslo Oslo Norway

   Research Institute of Internal Medicine Oslo University Hospital Oslo Norway

4. Jonas Øgaard

   Oslo University Hospital · University of Oslo

   Affiliation as printed

   Norwegian PSC Research Center, Oslo University Hospital and Institute of Clinical Medicine University of Oslo Oslo Norway

   Research Institute of Internal Medicine Oslo University Hospital Oslo Norway

5. Marte Kathrine Viken

   Oslo University Hospital · University of Oslo

   Affiliation as printed

   Department of Immunology University of Oslo and Oslo University Hospital Oslo Norway

   Department of Medical Genetics University of Oslo and Oslo University Hospital Oslo Norway

6. Cynthia S. M. Kramer Aachen Department of Immunology Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology Leiden University Medical Center Leiden The Netherlands

7. Michael Eikmans Aachen Department of Immunology Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology Leiden University Medical Center Leiden The Netherlands

8. Thomas Kroneis

   Medical University of Graz

   Affiliation as printed

   Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center Medical University of Graz Graz Austria

9. Katja Sallinger

   Medical University of Graz

   Affiliation as printed

   Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center Medical University of Graz Graz Austria

10. Sami B. Kanaan
    Affiliation as printed

    Chimerocyte, Inc. Seattle Washington USA

11. Meryam Sugulle

    Oslo University Hospital · University of Oslo

    Affiliation as printed

    Division of Obstetrics and Gynaecology Oslo University Hospital Oslo Norway

    Institute for Clinical Medicine, Faculty of Medicine University of Oslo Oslo Norway

12. Daniel Pitz Jacobsen corresponding

    Oslo University Hospital · University of Oslo

    Affiliation as printed

    Division of Obstetrics and Gynaecology Oslo University Hospital Oslo Norway

    Institute for Clinical Medicine, Faculty of Medicine University of Oslo Oslo Norway