Although, there is evidence for a role of MICA, HLA-E and EPCR in vascular transplant biology and immunology, genotyping is not routinely achieved and correlation between polymorphism and endothelial phenotype has not yet been examined. In this study, we examined the frequency and distribution of the various alleles for the non-classical MHC I genes MICA and HLA-E, and the MHC-related EPCR gene among a cohort of transplant donors (n=90). Genotyping was performed on genomic DNA issued from primary cultures of endothelial cells (ECs) established and prospectively stored at the time of transplantation and cell cultures were used to investigate MICA, HLA-E and EPCR mRNA and protein expression in relation to gene polymorphisms. For MICA, 31 different alleles were found and MICA*008 was the most frequent allele (34.53%), followed by MICA*004 (9.52%), MICA*00201 (7.14%), MICA*010 (7.14%), MICA*09 (6.55%) and MICA*011 (5.35%). Consistently, allelic frequency for MICA A5.1 mutation, mostly associated with MICA*008, was 37.3% in our cohort. We found that MICA A5.1 strongly increases MICA expression on donors ECs promoting recipients alloimmunisation. For HLA-E, 3 alleles were found, HLA-E*0101 (53.50%), *01031 and *01032 (both 46.50%). Homozygous *0101 and *0103 were 28.45% and 19.45%, respectively while heterozygous *0101/*0103 account for 51.20%. EPCR is a regulatory factor of hemostasis and a ligand for some gamma/deltaT cells, 14.3% of our donors carry one A3 allele (A1/A3 or A2 /3) and a single A3/A3 homozygous was found in our cohort indicating that this genotype is rare (1.2%). Although EPCR A3 allele was not associated with higher EPCR level on donors ECs, plasma level of sEPCR was significantly elevated in transplant donors carrying the A3 haplotype. Overall, the most common and equally represented genotypes were HLA-E*101/*103, MICAWT/A5.1 EPCR A/A and HLA-E*101/*103, MICAWT/WT EPCR A/A (overall 30.9% of transplant donors) feature EC pattern.of immunoregulatory molecules contributing to innate and alloresponses.
To cite this abstract in AMA style:Charreau B, Gerard N, Tonnerre P, Gavlovsky P, Pabois A, Guitton C. Integrated Analysis of MHC Class I-Like (MICA, HLA-E and EPCR) Genetic Diversity in Kidney Transplant Donors and Graft’s Endothelial Cell Phenotype [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/integrated-analysis-of-mhc-class-i-like-mica-hla-e-and-epcr-genetic-diversity-in-kidney-transplant-donors-and-grafts-endothelial-cell-phenotype/. Accessed December 4, 2020.
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