Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Purpose: Acute rejection (AR) still affects 8-14% of kidney transplants and rates of 10-year graft loss remain unchanged in part due to chronic rejection (CR). Yet, the mechanisms linking acute and chronic rejection remain poorly understood. We hypothesized that in-depth analysis of tissue gene expression could reveal biological insights into these mechanisms and identify networks of injury/inflammation indicative of graft failure.
Methods: 231 biopsies collected from 2005-2011 per protocol or 'for cause' were histologically phenotyped as AR, CR or excellent functioning allografts (TX), and profiled with Affymetrix HT 133 PM Plus DNA microarrays. HLA matching and additional long term outcome data were obtained from UNOS by approved request. Differentially expressed genes were analyzed with multiple unbiased functional pathway mapping and gene enrichment tools. Clusters of genes with high co-expression across samples were grouped and labeled by unifying biological functions to reveal new endophenotypes.
Conclusions: Co-expression network analysis revealed enrichment of a set of common immune processes for both AR and CR demonstrating their link to ineffective therapy. T cell driven immunity, specifically effector functions of helper and cytotoxic T lymphocytes (CTLs) and NK cells plus interferon-gamma cytokine effects were clearly evident. Evidence for B cell infiltration across AR and CR samples was heterogenous. The up-regulation of a cluster of tightly-correlated injury and inflammation genes, including lipocalin-2 (LCN2) and serpin peptidase inhibitor (SERPINA3), defined a molecular endophenotype in biopsies predictive of graft failure by CR >5 years later.
To cite this abstract in AMA style:Modena B, Kurian S, Friedewald J, Harrison F, Gelbart T, Head S, Abecassis M, Salomon D. Gene Expression of Kidney Biopsies Reveals Common Mechanisms of Rejection and a Cluster of Co-Expressed Genes Predictive of Long-term Outcomes [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/gene-expression-of-kidney-biopsies-reveals-common-mechanisms-of-rejection-and-a-cluster-of-co-expressed-genes-predictive-of-long-term-outcomes/. Accessed February 26, 2020.
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