Association of HLA-E Polymorphism with Severe Bacterial Infection and Early Transplant-Related Mortality in Matched Unrelated Bone Marrow Transplantation

Abstract

Despite prophylactic measures, susceptibility to severe infections in patients who had undergone bone marrow transplantation (BMT) is quite variable. To evaluate the potential role of human leukocyte antigen (HLA)-E polymorphism on the incidence of early infections, we analyzed 77 unrelated-donor (UD) BMT pairs identically matched for classical HLA class I and class II alleles. Multivariate analysis taking into account the patient-, donor- and transplant-related factors showed that bacterial infections and transplant-related mortality (TRM) at day 180 were high when the donor genotype was HLA-E*0101/E*0101 (hazard ratio [HR]=2.20; P=0.03 and HR=2.12, P=0.048, respectively), suggesting that homozygous state for HLA-E*0101 allele is a risk factor for early severe bacterial infections and TRM in UD-BMT.

Immunobiology of HLA Class-Ib Molecules in Transplantation

“…While HLAIa and HLA-II typing of both recipients and donors is routinely performed prior to organ transplant, the importance of typing HLA-Ib has not yet become widely acknowledged. It is interesting that HLA-E mismatches were observed in patients with matched HLA-Ia [59][60][61]. Paradoxically, the immunomodulatory mechanisms mediated by HLA-Ib can be expected to play a role in promoting graft acceptance [47,62], particularly in patients without viremia.…”

“…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].…”

Association Between HLA‐E *0101 Homozygosity and Recurrent Miscarriage in Egyptian Women

“…The selection of patients and control was carried out by systematic random sample. The mean age of the patients was 26.85 years (range [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38], and the average number of RM was 4 (range 3-6). All women selected were not having any previous live births (primary miscarriage).…”

“…Tamouza et al [26] was the first to report the association between HLA-E*0101 homozygosity and severe bacterial infections following HLA-matched unrelated donor hematopoietic stem cell transplantation and concluded that the presence of HLA-E*0101 allele could lead to inefficient presentation of bacterial peptides by the donor-derived antigen-presenting cells. Moreover, the increased frequency of HLA-E*0103 homozygosity observed in patients with nasopharyngeal cancer may provide enhanced inhibitory signals to NK cells that allow tumour escape [24].…”

“…The hypothesis of HLA-E allele homozygosity association with diseases was reported before in type 1 diabetes mellitus [23], nasopharyngeal carcinoma [24], HIV [25] and post-transplant complications [26,27]. Tamouza et al [26] was the first to report the association between HLA-E*0101 homozygosity and severe bacterial infections following HLA-matched unrelated donor hematopoietic stem cell transplantation and concluded that the presence of HLA-E*0101 allele could lead to inefficient presentation of bacterial peptides by the donor-derived antigen-presenting cells.…”