Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Recipients of an ABO incompatible transplant have circulating anti-AB antibodies, A and/or B antigens expressed on endothelium and usually C4d deposition on the endothelium, yet with adequate immunosuppressive treatment, this seldom leads to antibody-mediated rejection. This study investigated the mechanisms protecting the allograft from anti-AB antibody-mediated injury by gene expression analysis using RNA sequencing. We compared ABO-incompatible (ABOi) (4 cases, C4d-positive) and ABO-compatible (ABOc) (4 controls, C4d-negative) surveillance biopsies with normal histology in order to reduce differences in transcript expression associated with clinical events and to keep variation between samples to a minimum.
Initial analysis failed to identify any differentially expressed genes between the two groups. Removal of 40% of the lowest expressing genes allowed a less stringent correction for multiple testing and yielded 118 differentially expressed genes. Using a gene specific dispersion rate yielded 164 differentially expressed genes, resulting in 286 genes identified with differential expression between ABOi and ABOc groups. Of these, 136 were down regulated in the ABOi group and 150 were up-regulated.
Differentially expressed genes were compared to the pathogenesis-based transcript sets, previously defined by the Alberta Transplant Applied Genomic Centre. There was no significant overlap between them, with a total of 4 genes identified (PTPRC, PLEKHG1, GUCY1A3, SGK2).
Gene ontology (GO) analysis to examine down-regulated genes in the ABOi group identified genes relating to positive regulation of immune system process, leukocyte activation, cell activation, regulation of cytokine production, lymphocyte activation, positive regulation of response to stimulus and defence response.
We interrogated our data for differentially expressed genes in apoptosis and complement regulation pathways. We found only one gene, PI3Kγ, in the apoptosis pathway.
Genes identified in this study do not correlate with previous studies but do indicate a reduction in expression of immune response associated genes, indicating that suppression of the immune system may be preventing graft loss. Differentially expressed genes need to be validated in an independent set of biopsies in order to confirm whether they are true markers of accommodation.
To cite this abstract in AMA style:McLean A, Dominy K, Sosinsky A, Mueller M, Galliford J, Cook T, Roufosse C. Use of RNA Sequencing for Discovery of Markers of Accommodation in Surveillance Biopsies from Recipients of an ABO-Incompatible Renal Transplant [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/use-of-rna-sequencing-for-discovery-of-markers-of-accommodation-in-surveillance-biopsies-from-recipients-of-an-abo-incompatible-renal-transplant/. Accessed January 23, 2020.
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