Early isolated v-lesion may not truly represent a rejection of kidney allograft
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ABSTRACT: Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Although Banff classification assesses isolated v-lesion (IV) as a T-cell mediated rejection, its origin and significance remain unclear. To help resolve if IV truly represents acute rejection, molecular study was performed. Transcriptome of early IV, T cell-mediated vascular rejection (TCMRV) and nonrejection histologic findings was compared using microarrays (Illumina Human HT-12 v4 Expression BeadChips). The enrichment of deregulated genes was analysed using DAVID. Differential gene expression analysis identified 310 genes to be deregulated in TCMRV compared to IV. Gene enrichment analysis categorized deregulated genes to be associated with immune and inflammatory response. Principal component and unsupervised hierarchical cluster analysis revealed clear distinction of TCMRV samples but showed similarity of IV with control group. RT-qPCR validation on external sample set (n=20) confirmed upregulation of genes involved in immune response in TCMRV compared to IV. Based on stepwise logistic regression SLA2 gene represented the strongest group classifier [OR 0.106 (95 % CI 0.01- 0.774), p=0.03] with ROC AUC 0.906 [95% CI (0.769-1.0), p=0.003)]. IV reveals weak immunologic signature compared to TCMRV but shows similarity with non-rejection findings. Early IV in a DSA- and C4d- negative patients may feature non-rejection origin and reflect injury distinct from alloimmune response. Study calls for reassessment of current Banff histopathology criteria which considers an intimal arteritis to be TCMR irrespective of TI and supports use of molecular diagnostics as a part of integrative approach.
ORGANISM(S): Homo sapiens
PROVIDER: GSE114712 | GEO | 2018/05/22
REPOSITORIES: GEO
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