HLA‐E genotyping and its relevance in kidney transplantation outcome

Abstract

HLA-E, a class I nonclassical HLA molecule, is expressed in all tissues and is involved in the regulation of both innate (by interaction with the CD94/NKG2 receptor expressed mainly in NK cells) and adaptive immunity (by interaction with T CD8 + cells), suggesting a possible role in the solid organ transplantation context. Transplanted patients with chronic kidney disease and their respective donors (N = 107 pairs) were genotyped for exons 2 and 3 of the HLA-E locus by sequence-based typing (SBT). Groups' genotype frequencies were compared regarding episodes of clinical rejection by global G test, and binary logistic regression was made to demonstrate the contribution of genetic variables vs epidemiological variables. Comparisons of donors' genotype frequencies showed significant differences (P = .0230), revealing a protective profile of E*01:01/*01:01 compared to the other genotypes (P = .0099; OR = 0.3088; CI [95%] = 0.1333-0.7157). The same happened when the aforementioned genotype was combined with the E*01:01/*01:01 recipients' genotype (P = .0065; OR = 0.1760; CI [95%] = 0.0517-0.5987). A binary logistic regression analysis was performed, and, of all variables considered, only two were included in the resulting model (P = .007; R 2 Cox and Snell = 0.243; R 2 Nagelkerke = 0.328)-"End-Stage

HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation

“…The role of this functional dimorphism of HLA-E in solid organ transplantation has been studied in only a very limited number of studies. One study showed a protective role of the HLA-E*01:01/01:01 genotype of the donor for rejection in 107 kidney transplantation donor-recipient pairs ( 131 ). In another study, living-donor kidney recipients with HLA-E*01:01/01:01 experienced less BK polyoma virus (BKPyV) reactivation than recipients with other genotypes, and BKPyV-induced nephropathy occurred more frequently in recipients carrying the HLA-E*01:03 allele ( 132 ).…”

HLA‐E diversity unfolded: Identification and characterization of 170 novel HLA‐E alleles

“…The potential impact of this dimorphism has been studied for various diseases with inconsistent results 8,10 . In kidney transplantation, HLA‐E*01:01 homozygosity of the recipient and/or donor seems to be favorable 11,12 . Recently, the dimorphism's influence on hematopoietic stem cell transplantation has been analyzed in 1840 patients.…”