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

Tamouza, Ryad; Busson, Marc; Rocha, Vanderson; Fortier, Catherine; Haddad, Y.; Brun, Marion; Boukouaci, Wahid; Bleux, Hélène; Socié, Gérard; Krishnamoorthy, Rajagopal; Toubert, Antoine; Gluckman, Éliane; Charron, Dominique

doi:10.1097/01.tp.0000244598.92049.dd

Cited by 55 publications

(50 citation statements)

References 33 publications

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“…Moreover, an association of recipient HLA-E*0103 homozygosity with improved likelihood of patient overall survival has been observed (Bogunia-Kubik et al 2009, which concurs with the results of Tamouza et al (2006) and Danzer et al (2009). They have observed that the presence of HLA-E*0103 allele in donors, either in homozygous or heterozygous state, is associated with increased survival rate expressed by decreased TRM and decreased risk of acute GvHD (Danzer et al 2009;Tamouza et al 2006). Other studies have also confirmed the anti-GvHD effect (Ludajic et al 2009).…”

Section: Potential Role Of Hla-e and Cd94/nkg2a In Transplantation Ofsupporting

confidence: 79%

“…Minor histocompatibility antigens are presented primarily by classical HLA molecules and such complexes may activate T cells. It is hypothesized that either HLA-E outcompetes classical HLA proteins in mHags binding and disrupts the classical pathway, or it binds non-standard mHags peptides that could specifically mediate graft-versus-leukemia (GvL) rather than GvHD (Tamouza et al 2006). …”

Section: Potential Role Of Hla-e and Cd94/nkg2a In Transplantation Ofmentioning

confidence: 99%

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Clinical Significance of the HLA-E and CD94/NKG2 Interaction

Iwaszko

Bogunia‐Kubik

2011

Arch. Immunol. Ther. Exp.

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HLA-E belongs to the non-classical HLA (class Ib family) broadly defined by a limited polymorphism and a restricted pattern of cellular expression. So far, only two functional alleles differing at only one amino acid position (non-synonymous mutation) in the α2 heavy chain domain, where an arginine in position 107 in HLA-E*0101 is replaced by a glycine in HLA-E*0103, have been reported. The interaction between non-classical HLA-E molecule and CD94/NKG2A receptor plays a crucial role in the immunological response involving natural killer (NK) cells and cytotoxic T lymphocytes. All proteins forming CD94/NKG2 receptors are encoded by genes situated in the same cluster on chromosome 12, allowing tight control over the order of their expression. The inhibitory members of the NKG2 receptor family are available on the cell surface before activating the members to prevent autoimmune incidents during immune cells' ontogenesis. In the present review, the potential role of this interaction in viral infection, pregnancy and transplantation of allogeneic hematopoietic stem cells (HSC) is presented and discussed. The review will also include the effect of HLA-E polymorphism on the outcome of HSC transplants in humans.

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Section: Potential Role Of Hla-e and Cd94/nkg2a In Transplantation Ofsupporting

confidence: 79%

Section: Potential Role Of Hla-e and Cd94/nkg2a In Transplantation Ofmentioning

confidence: 99%

Clinical Significance of the HLA-E and CD94/NKG2 Interaction

Iwaszko

Bogunia‐Kubik

2011

Arch. Immunol. Ther. Exp.

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“…This further confirms the existence of weak linkage disequilibrium between the classical HLA and HLA-E loci [59]. In HLA-E-matched allogeneic HSCT, the HLA-E*01:03/01:03 homozygous genotype has a protective role since it is associated with a lower frequency of acute and chronic GvHD, and it is associated with improved overall survival compared with other HLA-E genotypes [66,67]. Therefore, lower HLA-E expression on allograft-associated with the HLA-E*01:01 homozygous state [19] may lead to complications such as GvHD because the recipient may be less capable of inhibiting immune cells through CD94/ NKG2A receptors.…”

Section: Hla-ib In Graft-versus-host Diseasesupporting

confidence: 62%

“…Therefore, HLA-E*01:03 homozygous recipients may be better graft "acceptors" than HLA-E*01:01 patients provided that the allograft is devoid of viremia. Withal, a HLA-E genotype match should be beneficial in transplantation because the HLA-E homozygous state has been shown to be associated with transplantation outcomes, especially in BMT and HSCT [59,66,67].…”

Section: Hla-ib: Role In Histocompatibilitymentioning

confidence: 99%

Immunobiology of HLA Class-Ib Molecules in Transplantation

Jucaud¹

2015

SOJI

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“…Recent reports have shown that the homozygous state for the HLA-E*0103 allele in allo-SCT recipients, which results in a higher cell surface expression of HLA-E, is associated with a lower incidence of transplant-related mortality (54) and an improved overall survival (55). These findings suggest a protective role for HLA-E against endothelial damage by NK cells.…”

Section: Discussionmentioning

confidence: 54%

The Rapid Induction of HLA-E Is Essential for the Survival of Antigen-Activated Naive CD4 T Cells from Attack by NK Cells

Takao

Ishikawa

Yamashita

et al. 2010

The Journal of Immunology

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Increasing evidence shows that NK cells regulate adaptive immunity, but the underlying mechanisms are not well understood. In this study, we show that activated human NK cells suppress autologous naive CD4 T cell proliferation in response to allogeneic dendritic cells (DCs) by selectively killing Ag-activated T cells. Naive CD4 T cells, which were initially resistant to NK cell-mediated cytotoxicity, became substantially susceptible to NK cells within a day after priming with DCs. Ag-activated T cells showed various degrees of susceptibility to NK cells. After 1 d of priming with LPS-matured DCs, T cells were less susceptible to NK cells than were T cells primed with TNF-α–matured DCs. Subsequently at day 3, Ag-activated T cells regained resistance to NK cells. The level of HLA-E expression on Ag-activated T cells was closely correlated with resistance to NK cells. HLA-E was highly expressed at day 1 by T cells primed with LPS-matured DCs but not by T cells primed with TNF-α–matured DCs. An Ab blockade revealed a critical role for the HLA-E–NKG2A interaction in the protection of Ag-activated T cells from NK cells. Collectively, this study demonstrates that NK cells impact adaptive immunity through the finely controlled kinetics of HLA-E expression on T cells. Thus, HLA-E may be a new target for immunoregulation.

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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: 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.

Cited by 55 publications

References 33 publications

Clinical Significance of the HLA-E and CD94/NKG2 Interaction

Clinical Significance of the HLA-E and CD94/NKG2 Interaction

Immunobiology of HLA Class-Ib Molecules in Transplantation

The Rapid Induction of HLA-E Is Essential for the Survival of Antigen-Activated Naive CD4 T Cells from Attack by NK Cells

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