Impact of High-Frequency HLA Haplotypes on Clinical Cytomegalovirus Reactivation in Allogeneic Hematopoietic Stem Cell Transplantation

HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation

Research output: Contribution to journalArticlepeer-review

Abstract

Some studies support the hypothesis that HLA genes and haplotypes evolved by natural selection through their protective abilities against specific infectious pathogens. However, very little is known regarding the impact of high-frequency HLA haplotypes on the risk of relevant infectious diseases among a given ethnic group. We evaluated the impact of high-frequency HLA haplotypes on cytomegalovirus (CMV) reactivation and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a Japanese population as a model of infectious disease that has coexisted with humans. A total of 21,127 donor-patient pairs were analyzed. HLA-A-B-DRB1 haplotypes were estimated using the maximum probability algorithm. Seven haplotypes with >1% frequency were defined as high-frequency haplotypes (HfHPs). Homozygotes of HfHP and heterozygotes had significantly lower risk of CMV reactivation and infection (hazard ratio [HR] = 0.88, P =.009 and HR = 0.93, P =.003, respectively) than homozygotes of low-frequency HLA haplotypes (LfHPs). In subgroup analyses of a different donor source, these associations were statistically significant in unrelated donor transplants. Finally, CMV risk for homozygotes and heterozygotes of each HfHP was compared with that of homozygotes of LfHPs. The 2 most predominant HfHP groups (A*24:02-B*52:01-DRB1*15:02 group and A*24:02-B*07:02-DRB1*01:01 group) had a significantly lower risk of CMV reactivation and infection (HR = 0.86, P <.001 and HR = 0.91, P =.033, respectively). Our findings suggest that HfHPs may be protective against CMV reactivation and infection and that increased care regarding CMV reactivation and infection may be necessary for patients with LfHP after allo-HSCT.

Original languageEnglish
JournalBiology of Blood and Marrow Transplantation
DOIs
Publication statusAccepted/In press - 2019

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Fingerprint Dive into the research topics of 'Impact of High-Frequency HLA Haplotypes on Clinical Cytomegalovirus Reactivation in Allogeneic Hematopoietic Stem Cell Transplantation'. Together they form a unique fingerprint.

Cite this