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 journalArticle

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 - Jan 1 2019

Fingerprint

Hematopoietic Stem Cell Transplantation
Cytomegalovirus
Haplotypes
Cytomegalovirus Infections
Homozygote
Heterozygote
Communicable Diseases
Tissue Donors
Unrelated Donors
HLA-A Antigens
HLA-B Antigens
Genetic Selection
Ethnic Groups

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

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.

In: Biology of Blood and Marrow Transplantation, 01.01.2019.

Research output: Contribution to journalArticle

@article{1729a7e0ddae4b57b88a9e92c4ead2cf,
title = "Impact of High-Frequency HLA Haplotypes on Clinical Cytomegalovirus Reactivation in Allogeneic Hematopoietic Stem Cell Transplantation",
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.",
author = "{HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation} and Takakazu Kawase and Hidenori Tanaka and Hiroto Kojima and Naoyuki Uchida and Kazuteru Ohashi and Takahiro Fukuda and Yukiyasu Ozawa and Kazuhiro Ikegame and Tetsuya Eto and Takehiko Mori and Toshihiro Miyamoto and Michihiro Hidaka and Souichi Shiratori and Minoko Takanashi and Yoshiko Atsuta and Tatsuo Ichinohe and Yoshinobu Kanda and Junya Kanda",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.bbmt.2019.07.042",
language = "English",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Impact of High-Frequency HLA Haplotypes on Clinical Cytomegalovirus Reactivation in Allogeneic Hematopoietic Stem Cell Transplantation

AU - HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation

AU - Kawase, Takakazu

AU - Tanaka, Hidenori

AU - Kojima, Hiroto

AU - Uchida, Naoyuki

AU - Ohashi, Kazuteru

AU - Fukuda, Takahiro

AU - Ozawa, Yukiyasu

AU - Ikegame, Kazuhiro

AU - Eto, Tetsuya

AU - Mori, Takehiko

AU - Miyamoto, Toshihiro

AU - Hidaka, Michihiro

AU - Shiratori, Souichi

AU - Takanashi, Minoko

AU - Atsuta, Yoshiko

AU - Ichinohe, Tatsuo

AU - Kanda, Yoshinobu

AU - Kanda, Junya

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85072271025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072271025&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2019.07.042

DO - 10.1016/j.bbmt.2019.07.042

M3 - Article

C2 - 31400501

AN - SCOPUS:85072271025

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

ER -