title: Association of HLA-G low expressor genotype with severe acute graft-versus-host disease after sibling bone marrow transplantation.
abstract: 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 14 bp 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratoire d'Immunologie et d'Histocompatibilité and INSERM, UMRS 940, Hôpital Saint-Louis Paris, France.
authors.forename: Wahid
authors.initials: W
authors.lastname: Boukouaci
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: Catherine
authors.initials: C
authors.lastname: Fortier
authors.forename: Kahina
authors.initials: K
authors.lastname: Amokrane
authors.forename: Régis Peffault
authors.initials: RP
authors.lastname: de Latour
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza