Immunologic Research

, Volume 58, Issue 2–3, pp 249–258 | Cite as

Clinical impact of H-Y alloimmunity

  • Rakesh Popli
  • Bita Sahaf
  • Hideki Nakasone
  • Joyce Yeuk Yu Lee
  • David B. MiklosEmail author


H-Y antigens are a group of minor histocompatibility antigens encoded on the Y-chromosome with homologous H-X antigens on the X-chromosome. The disparate regions of the H-Y antigens are highly immunogenic and play an important role in understanding human alloimmunity. In this review, we investigate the history of H-Y antigen discovery along with their critical contributions in transplantation and pregnancy. In hematopoietic cell transplantation, male recipients with female donors who become seropositive for B-cell responses as H-Y antibodies following transplantation have increased rates of chronic graft-versus-host disease and decreased rates of relapse. Conversely, female patients who receive male kidney allografts are more likely than other gender combinations to develop H-Y antibodies and reject their allografts. Finally, in the setting of pregnancy, mothers who initially gave birth to boys are more likely to have subsequent pregnancy complications, including miscarriages, in association with H-Y antibody development. H-Y antigens continue to serve as a model for alloimmunity in new clinical scenarios. Our development of more sensitive antibody detection and next-generation DNA sequencing promises to further advance our understanding and better predict the clinical consequences of alloimmunity.


H-Y antigen Graft-versus-host disease Graft rejection Pregnancy complications Alloimmunity Kidney transplantation 



We would like to thank Fang Wu and John Coller, Director of the Stanford Functional Genomics Facility, for their technical assistance, along with Carl Grumet and Joanne Otani for their helpful comments and suggestions. This work was supported by National Heart Lung and Blood Institute Grant R21 HL084318, National Cancer Institute Grant P01 CA049605 and Stanford University Cancer Institute Support Grant 1P030CA124435-01.

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Rakesh Popli
    • 1
  • Bita Sahaf
    • 1
  • Hideki Nakasone
    • 1
  • Joyce Yeuk Yu Lee
    • 1
  • David B. Miklos
    • 1
    Email author
  1. 1.Division of Blood and Marrow Transplantation, Department of MedicineStanford University School of MedicineStanfordUSA

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