Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: A previous gene expression microarray study in pre-implantation biopsies (PIB) from kidneys of adult deceased donors (D) showed association between high class II HLA genes expression and low (eGFR < 45 ml/min) 1-year (Y) graft function (GF). Further analysis on HLA-DQB1 and -DQB2 expression disclosed that the association was restricted to transplants with kidneys from D up to 49 years of age (young D) (Hum Immunol, 2018). The aim of the present study was to investigate the relationship between HLA-DPB1 expression in PIB and late GF and the impact of the single-nucleotide polymorphism (SNP) rs9277534, located in the 3’ untranslated region of DPB1 gene, on DPB1 expression and on GF. The rs9277534 G allele has been shown to be associated with high DPB1 expression in lymphocytes.
*Methods: The study was conducted in two cohorts from the previous study. In the microarray cohort, DPB1 expression data of 53 PIBs (GeneChip® Human Gene 1.0 ST Arrays, Affymetrix) were studied concerning 5-Y GF. In the validation cohort, DPB1 expression (RT-PCR, TaqMan Assay®) was analyzed in 109 PIBs, regarding 1- and 2-Y GF. DPB1 typing (PCR-SSO) and SNP determination (TaqMan Assay®) were performed in 120 recipient-donor pairs.
*Results: The microarray study showed higher DPB1 expression in PIB from young D in cases that presented low 5-Y GF (p=0.012). In the validation cohort, at 1-Y, the association was present in transplants with young D (p=0.047), but not with old D (p=0.3). Considering the 2-Y GF, however, the association was also present in transplants with old D (p=0.033). Regarding the SNP, DPB1 expression was higher in PIB of kidneys from rs9277534 GG donors than from AA donors (p=0.006). The proportion of cases with low 1- and 2-Y GF was higher in transplants with the high expression allele (G) in the DPB1 mismatch (MM) allele in transplants with young and old D, but the difference reached statistical significance only for 2-Y GF in transplants with young D.
*Conclusions: (1) there is association between increased expression of DPB1 in PIB and poor late GF, mainly in transplants with young D; (2) homozygosity for the high expression rs9277534 G allele associates with higher DPB1 expression in PIB; (3) the data suggest that the presence of the G allele in the mismatched DPB1 allele could be associated with low GF.
To cite this abstract in AMA style:Mine KL, Mourão TB, Felipe C, Rampim GF, Medina-Pestana JO, Tedesco-Silva H, Gerbase-DeLima M. Relationship between HLA-DPB1 Gene Expression in Pre-Implantation Kidney Biopsies, Rs9277534 Polymorphism, and Late Graft Function [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/relationship-between-hla-dpb1-gene-expression-in-pre-implantation-kidney-biopsies-rs9277534-polymorphism-and-late-graft-function/. Accessed December 13, 2019.
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