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The Regulation of IFN Type I Pathway Related Genes RSAD2 and ETV7 Specifically Indicate Antibody-Mediated Rejection After Kidney Transplantation.

Clinical Transplantation 2018 October 21
CONTEXT: Antibody-mediated rejection (ABMR) after kidney transplantation (KTx) remains the crucial obstacle to successful long-term graft function. The identification of gene signatures involved in ABMR could grant the basis for better prevention and treatment strategies.

OBJECTIVE: The identification of gene signatures in whole blood cells specific for ABMR after kidney transplantation.

MATERIAL AND METHODS: Total RNA from blood cells of 16 kidney transplanted patients with ABMR, stable graft function (SGF) and with T-cell mediated rejection (TCMR) was isolated. Gene expression was determined by high-throughput sequencing followed by validation and analyses of differentially expressed candidates on mRNA level and on protein level in a large patient cohort (n=185) in patients with SGF, urinary tract infection (UTI), borderline rejection (BL), TCMR, ABMR and interstitial fibrosis and tubular atrophy (IFTA).

RESULTS: From the 570 genes detected, 111 discriminated ABMR from SGF and TCMR. A distinct enrichment of IFN type I and type II signature gene set was observed. The expression of candidate genes IFIT1, ETV7 and RSAD2 distinguished ABMR patients from patients with SGF and also TCMR, whereas ETV7 and RSAD2 differentiated ABMR also from BL.

CONCLUSION: The IFN-inducible genes (IFIGs) ETV7 and RSAD2 represent specific biomarkers for ABMR episodes after kidney transplantation. This article is protected by copyright. All rights reserved.

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