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.

Abstract

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.

• Authors: Ryad Tamouza, Marc Busson, Vanderson Rocha, Catherine Fortier, Yacine Haddad, Manuel Brun, Wahid Boukouaci, Hélène Bleux, Gérard Socié, Rajagopal Krishnamoorthy, Antoine Toubert, Eliane Gluckman, Dominique Charron
• Journal: Transplantation (Transplantation) Vol. 82 Issue 11 Pg. 1436-40 (Dec 15 2006) ISSN: 0041-1337 [Print] United States
• PMID: 17164714 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA Antigens
• HLA-E antigen
• Histocompatibility Antigens Class I

Topics

• Acute Disease
• Adolescent
• Adult
• Alleles
• Child
• Child, Preschool
• Female
• Genotype
• Graft vs Host Disease (genetics, mortality)
• HLA Antigens (genetics)
• Hematopoietic Stem Cell Transplantation
• Histocompatibility Antigens Class I
• Homozygote
• Humans
• Male
• Middle Aged
• Siblings