The role of metallothionenins and Slc genes in accommodation in ABOincompatible transplantation

ABSTRACT: Both present hemagglutinins and anti HLA antibodies bind to vascular endothelial cells in kidney transplantation, however in some patients this antibody-endothelial interaction is not associated with obvious tissue injury. Mechanisms of this phenomenon called accommodation remain poorly understood. Illumina Human HT-12 v4 Expression BeadChips whole renal transcriptome was evaluated in 3-months protocol biopsies with isolated C4d staining in otherwise stable ABO incompatible and HLA incompatible DSA positive kidney grafts (n=18) as well as in C4d negative HLA compatible grafts with normal histological findings (n=8). Top differently regulated genes were further validated using RT-qPCR at the independent patient cohort (n=24). GO terms with the highest fold enrichment revealed by gene annotation analysis of deregulated genes between ABOi and HLAi groups were represented by cadmium ion binding (p<0.01), apical plasma membrane (p<0.01) and anion transmembrane transporter activity (p<0.05). Majority of deregulated genes between both groups belongs to metallothioneins (MT) and solute carrier family (Slc) genes. The decreased expression of 5 Slc family genes (SLC4A1; SLC4A9; SLC17A3; SLC12A3; SLC30A2) and 3 metallothioneins of class1 (MT1F, MT1G and MT1X) in ABOi compared to HLAi group was verified by RT-qPCR. The most deregulated genes in C4d negative compared with C4d positive cohorts were those included in GO term “mitochondrion” which suggests the activation of metabolism in complement activation. In conclusion, hemagglutinin- and anti-HLA antibody-endothelial interactions and complement activation lead to different regulation of metallothioneins and distinct solute carrier family genes, which suggests its specific role in the accommodation phenomenon.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109346 | GEO | 2018/01/19

REPOSITORIES: GEO