In a previous gene expression microarray study in pre-implantation biopsies (PIB) from kidneys of 53 deceased donors (GeneChip® Human Gene 1.0 ST Arrays, Affymetrix; GEO accession number GSE54888), we observed association between higher expression levels of HLA class II, but not class I, genes and poor (eGFR <45 ml/min/1.73 m²) graft function (GF), at 1-Y post-transplant. In the present study we aimed to: (1) investigate the relationship between DPB1 expression in PIB from the microarray study and 5-Y GF; (2) validate, in a different cohort (N=109), by Real Time-PCR (RT-PCR), the association between HLA-DPB1 expression in PIB and 1-Y GF; (3) investigate the relationship between the single-nucleotide polymorphism (SNP) rs9277534, located in the 3' untranslated region of DPB1 and expression of DPB1 in PIB; (4) investigate the impact, on the 1-Y GF, of the presence, in the donor, of the high expression rs9277534 allele (G) in transplants with one or two DPB1 mismatches (MM). RT-PCR was performed with TaqMan Assays^® (Applied Biosystems) Hs00157955_m1 (HLA-DPB1) and Hs00920495_m1 (TBP control gene); HLA-DPB1 typing was done with PCR-SSO (One Lambda); rs9277534 alleles were determined with the TaqMan Assay^® (Applied Biosystems) C_29841700_20. Results: the higher DPB1 expression in PIB from the microarray study was associated with poor 5-Y GF (p=0.03); the association between increased DPB1 expression in PIB and poor 1-Y GF was confirmed in a different cohort with 51 cases with poor and 58 cases with good GF (p=0.037); PIB from donors homozygous for the high DPB1 expression allele (rs9277534G) (N=19) presented higher DPB1 expression levels as compared to PIB from donors homozygous for the low DPB1 expression allele (rs9277534A) (N=44) (p=0.008); no significant difference in the proportion of cases with poor 1-Y GF was observed between transplants where the high or the low expression allele was present in the MM DPB1 antigen (58% vs 47% with poor 1-Y GF). Conclusions: (1) there is association between increased expression of HLA-DPB1 in PIB and poor 1- and 5-Y graft function; (2) despite the association of the rs9277534G allele with high DPB1 expression in PIB, the presence of this allele in the mismatched DPB1 allele was not associated with poor 1-Y GF.

CITATION INFORMATION: Mine K., Mourão T., Felipe C., Rampim G., Medina-Pestana J., Tedesco-Silva H., Gerbase-DeLima M. Increased Expression of HLA-DPB1 in Pre-Implantation Kidney Biopsies is Associated with Poor Late Graft Function Am J Transplant. 2017;17 (suppl 3).

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