Influence of major histocompatibility complex class I chain-related gene A polymorphisms on cytomegalovirus disease after allogeneic hematopoietic cell transplantation.
Allogeneic hematopoietic cell transplantation
Cytomegalovirus
Killer cell immunoglobulin-like receptors
Major histocompatibility complex class I chain-related gene A
Journal
Hematology/oncology and stem cell therapy
ISSN: 2589-0646
Titre abrégé: Hematol Oncol Stem Cell Ther
Pays: Saudi Arabia
ID NLM: 101468532
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
20
02
2019
revised:
18
09
2019
accepted:
27
10
2019
pubmed:
28
12
2019
medline:
8
10
2020
entrez:
28
12
2019
Statut:
ppublish
Résumé
Cytomegalovirus (CMV) infection and disease are common infectious complications after allogeneic hematopoietic cell transplantation (alloHCT). Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity. We hypothesized that MICA polymorphisms may influence CMV infection and disease incidence after alloHCT. We conducted a retrospective analysis of 423 adults at the Cleveland Clinic with hematologic malignancies treated with a matched related or unrelated donor alloHCT. CMV cases analyzed included a compositive of instances of viral copy replication above detection limits as well as any biopsy-proven tissue invasive disease episodes. Genotypes at the MICA-129 position have been categorized as weak (valine/valine; V/V), intermediate (methionine/valine; M/V), or strong (methionine/methionine; M/M) receptor affinity. In multivariable analysis, V/V donor MICA-129 genotype was associated with CMV infection and disease (hazard ratio [HR] = 1.40; 95% confidence interval [CI], 1.00-1.96; p = .05), but not MICA mismatch (HR = 1.38; 95% CI, 0.83-2.29; p = .22). There was no association of acute or chronic GVHD with MICA donor-recipient mismatch (HR = 1.05; 95% 95% CI, 0.66-1.68; p = .83 and HR = 0.94; 95% CI, 0.51-1.76; p = .85, respectively) or V/V donor MICA-129 genotypes (HR = 1.02; 95% CI, 0.79-1.31; p = .89 and HR = 0.89; 95% CI, 0.65-1.22; p = .47, respectively). These findings suggest that the donor MICA-129 V/V genotype with weak NKG2D receptor binding affinity is associated with an increased risk of CMV infection and disease after alloHCT.
Sections du résumé
OBJECTIVE/BACKGROUND
OBJECTIVE
Cytomegalovirus (CMV) infection and disease are common infectious complications after allogeneic hematopoietic cell transplantation (alloHCT). Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity. We hypothesized that MICA polymorphisms may influence CMV infection and disease incidence after alloHCT.
METHODS
METHODS
We conducted a retrospective analysis of 423 adults at the Cleveland Clinic with hematologic malignancies treated with a matched related or unrelated donor alloHCT. CMV cases analyzed included a compositive of instances of viral copy replication above detection limits as well as any biopsy-proven tissue invasive disease episodes. Genotypes at the MICA-129 position have been categorized as weak (valine/valine; V/V), intermediate (methionine/valine; M/V), or strong (methionine/methionine; M/M) receptor affinity.
RESULTS
RESULTS
In multivariable analysis, V/V donor MICA-129 genotype was associated with CMV infection and disease (hazard ratio [HR] = 1.40; 95% confidence interval [CI], 1.00-1.96; p = .05), but not MICA mismatch (HR = 1.38; 95% CI, 0.83-2.29; p = .22). There was no association of acute or chronic GVHD with MICA donor-recipient mismatch (HR = 1.05; 95% 95% CI, 0.66-1.68; p = .83 and HR = 0.94; 95% CI, 0.51-1.76; p = .85, respectively) or V/V donor MICA-129 genotypes (HR = 1.02; 95% CI, 0.79-1.31; p = .89 and HR = 0.89; 95% CI, 0.65-1.22; p = .47, respectively).
CONCLUSION
CONCLUSIONS
These findings suggest that the donor MICA-129 V/V genotype with weak NKG2D receptor binding affinity is associated with an increased risk of CMV infection and disease after alloHCT.
Identifiants
pubmed: 31881183
pii: S1658-3876(19)30104-9
doi: 10.1016/j.hemonc.2019.10.001
pii:
doi:
Substances chimiques
H-2 Antigens
0
H-2K(K) antigen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
32-39Informations de copyright
Copyright © 2019 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest There are no conflicts of interest to report.