HLA-E genotyping and its relevance in kidney transplantation outcome.

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; R2 Cox and Snell = 0.243; R2 Nagelkerke = 0.328)- "End-Stage Renal Disease" and "HLA class II Mismatches." A protective profile (E*01:01/*01:01) was observed between the recipients and donors, suggesting a possible impact of the HLA-E genotype in rejection episodes.

High-resolution characterization of 12 classical and non-classical HLA loci in Southern Brazilians.

The human leukocyte antigen (HLA) are the most polymorphic genes in the human genome. Because of their importance for antigen recognition, HLA molecules play a central role in host defense and graft rejection upon transplantation. The aim of this study was to characterize allelic diversity of the classical HLA genes HLA-A, -B, -C, -DRA, -DRB1, -DQA1, -DQB1, -DPA1, -DPB1, and the non-classical class I genes HLA-E, -F and -G at high-resolution for a population of predominantly European ancestry from Curitiba, Brazil. Genotyping of 108 individuals was performed by next-generation sequencing on the MiSeq platform and also by Sanger sequencing. The genotype distributions of all loci were in accordance with Hardy-Weinberg equilibrium (P > 0.05) and a total of 202 HLA variants at second field resolution were observed for the 12 loci. The strongest linkage disequilibrium (r2 = 1.0, P < 10-5 ) was observed for the following pairs of alleles: HLA-B*42:01:01 ~ HLA-DRB1*03:02:01; HLA-B*14:02:01 ~ HLA-C*08:02:01; B*42:01:01 ~ HLA-C*17:01:01; HLA-DRB1*03:01:01 ~ HLA-DQB1*02:01:01 ~ DRB1*03:01:01 ~ HLA-DQB1*02:01:01; DRB1*13:01:01~ HLA-DQB1*06:03:01 and HLA-DRB1*09:01:02 ~ HLA-DQA1*03:02. This is the first study to characterize all 12 HLA genes at high resolution in a single population. On the basis of the allelic frequencies of worldwide populations and principal component analysis, we confirmed the similarity of the study population to European and other Euro-descendant populations.