Homozygous status for HLA-E*0103 confers protection from acute graft-versus-host disease and transplant-related mortality in HLA-matched sibling hematopoietic stem cell transplantation.
BACKGROUND
The posttransplant period following hematopoietic stem cell transplantation (HSCT) is potentially high risk for developing survival-compromising complications, many of which are known to be under the control of immunogenetic factors. Given the dual role of human leukocyte antigen (HLA)-E molecules in innate and adaptive immune processes, we analyzed the impact of HLA-E polymorphism in genoidentical HSCT setting.


METHODS
We analyzed 187 HLA-genoidentical sibling pairs for HLA-E polymorphism. To explore its potential association with the incidence of acute and chronic graft versus host disease (aGVHD, cGVHD), severe infections, risk for transplant-related mortality (TRM), and overall survival, HLA-E locus was genotyped by a polymerase chain-reaction-sequence-specific primer (PCR-SSP) strategy.


RESULTS
Multivariate analysis, taking into account the patient-, donor- and transplant-related factors, showed that the incidence of aGVHD and TRM at day 180 were low when the genotype was HLA-E*0103/E*0103, either in the donor or in the recipient, the pairs being identical for HLA-E alleles (hazard ratio [HR]=0.71, P=0.009; and HR=0.42, P=0.04, respectively). We also found a trend towards association between E*0103 homozygosity and improved survival (P=0.05). There was no association between HLA-E polymorphism and incidence of severe infections.


CONCLUSIONS
These data suggest that the homozygous state for HLA-E*0103 allele behaves as a protective genetic factor against aGVHD and TRM and likely contributes to improved survival in HLA-genoidentical bone marrow transplantation.
Tamouza
Ryad
R
Assistance publique- Hôpitaux de Paris/Groupement Hôspitalier et Universitaire Nord, Institut Universitaire d'Hématologie, et Institut National de la Santé et de la Recherche Médicale U662, Hôpital Saint-Louis, Paris, France. tamouza@histo.chu-stlouis.fr
Busson
Marc
M
Rocha
Vanderson
V
Fortier
Catherine
C
Haddad
Yacine
Y
Brun
Manuel
M
Boukouaci
Wahid
W
Bleux
Hélène
H
Socié
Gérard
G
Krishnamoorthy
Rajagopal
R
Toubert
Antoine
A
Gluckman
Eliane
E
Charron
Dominique
D
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000401:mortality*; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D035781:Siblings; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens