Single Cell Transcriptomics of Human Native Kidney and Kidney Allografts
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE151671 | GEO | 2022/04/19
REPOSITORIES: GEO
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Project description:The aim of this study was to investigate correlations between early subclinical findings (10 and 90 day histology and gene expression data) and late outcomes (transplant glomerulopathy and graft loss) in positive crossmatch kidney transplants (+XMKTx). Our goal was threefold: first, to confirm that intragraft molecular changes at 12m post-transplant are associated with the observed histologic changes in SLK transplant recipients, compared with KTA transplant recipients; second, to ascertain whether specific molecular pathways/markers that are not accounted for by routine histology are differentially expressed in the kidney allografts of the SLK transplant recipients; and third, to determine whether a molecular signature that is uniquely associated with simultaneous liver transplantation can be identified in kidney allografts. Biopsy samples were from positive and negative crossmatch simultaneous liver-kidney transplant recipients (12 month protocol biopsies) were compared to control patient (positive and negative crossmatch) biopsies obtained at 12 months. This dataset is part of the TransQST collection.
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Project description:The aim of this study was to investigate correlations between early subclinical findings (10 and 90 day histology and gene expression data) and late outcomes (transplant glomerulopathy and graft loss) in positive crossmatch kidney transplants (+XMKTx). Our goal was threefold: first, to confirm that intragraft molecular changes at 12m post-transplant are associated with the observed histologic changes in SLK transplant recipients, compared with KTA transplant recipients; second, to ascertain whether specific molecular pathways/markers that are not accounted for by routine histology are differentially expressed in the kidney allografts of the SLK transplant recipients; and third, to determine whether a molecular signature that is uniquely associated with simultaneous liver transplantation can be identified in kidney allografts.
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Project description:We studied intragraft gene expression profiles of positive crossmatch (+XM) kidney transplant recipients who develop transplant glomerulopathy (TG) and those who do not. Whole genome microarray analysis and quantitative rt-PCR for 30 transcripts were performed on RNA from protocol renal allograft biopsies in 3 groups: 1) +XM/TG+ biopsies before and after TG; 2) +XM/NoTG; and 3) negative crossmatch kidney transplants (control). Microarray comparisons showed few differentially expressed genes between paired biopsies from +XM/TG+ recipients before and after the diagnosis of TG. Comparing +XM/TG+ and control groups, significantly altered expression was seen for 2,447 genes (18%) and 3,200 genes (24%) at early and late time points, respectively. Canonical pathway analyses of differentially expressed genes showed inflammatory genes associated with innate and adaptive immune responses. Comparing +XM/TG+ and +XM/NoTG groups, 3,718 probe sets were differentially expressed but these were over-represented in only 4 pathways. A classic accommodation phenotype was not identified. Using rt-PCR, the expression of inflammatory genes was significantly increased in +XM/TG+ recipients compared to control biopsies and to +XM/NoTG biopsies. In conclusion, pre-transplant DSA results in a gene expression profile characterized by inflammation and cellular infiltration and the majority of XM+ grafts are exposed to chronic injury. We analyzed gene expression from 2 groups of positive crossmatch kidney transplant recipients (+XM/TG+ and +XM/TG-). Patients in the +XM/TG+ group had 2 biopsies - prior to the development of transplant glomerulopathy on biopsy (Biopsy 1; cg=0; n=10) and after development of transplant glomerulopathy (Biopsy 2; cg>0; n=10). The +XM/TG- patients had only a Biopsy 2 (cg=0; n=11). A third patient group served as controls (n=10) and were from -XM recipients. This dataset is part of the TransQST collection.
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