Association of HLA-G low expressor genotype with severe acute graft-versus-host disease after sibling bone marrow transplantation

Wahid Boukouaci, Marc Busson, Catherine Fortier, Kahina Amokrane, Régis Peffault De Latour, Marie Robin, Rajagopal Krishnamoorthy, Antoine Toubert, Dominique Charron, Gérard Socié, Ryad Tamouza

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

27 Citations (Scopus)

Résumé

Background: Human leukocyte antigen-G (HLA-G) molecules play a prominent role in immune tolerance. Structurally similar to their classical HLA homologs, they are distinct by having high rate of polymorphism in the non-coding regions including a functionally relevant 14-base pair (bp) insertion/deletion (Ins/Del) allele in the 3' untranslated region (3'UTR), rarely examined in a hematopoietic stem cell transplantation (HSCT) setting. Here, we analyzed the potential impact of HLA-G Ins/Del dimorphism on the incidence of acute graft-versus-host disease (aGvHD), transplant-related mortality (TRM), overall survival (OS), and incidence of relapse after HSCT using bone marrow (BM) as stem cell source from HLA-matched donors. Methods: One hundred fifty-seven sibling pairs, who had undergone HSCT, were studied for the distribution of the HLA-G 14bp Ins/Del polymorphism using a polymerase chain reaction (PCR)-based technique. Potential genetic association with the incidence of aGvHD, TRM, and OS was analyzed by monovariate and multivariate analyses. Results: Monovariate analysis showed that the homozygous state for the 14-bp Ins allele is a risk factor for severe aGvHD (grade III and IV; P= 0.008), confirmed subsequently by multivariate analysis [hazard ratio (HR) = 3.5; 95% confidence interval (95%CI) = 1.3-9.5; P= 0.012]. We did not find any association between HLA-G polymorphism and the other studied complications. Conclusion: Our data suggest that the HLA-G low expressor 14 bp Ins allele constitutes a risk factor for the incidence of severe aGvHD in patients who received BM as stem cell source.

langue originaleAnglais
Numéro d'articleArticle 74
journalFrontiers in Immunology
Volume2
Numéro de publicationDEC
Les DOIs
étatPublié - 1 déc. 2011
Modification externeOui

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