16a7faef4af9397de77b387e9cfc98a4 pmc_33153205.pdf 884be01253bac642b558eb64bfe3e778854d45f7 pmc_33153205.pdf 4da3631e7a9ca18ed3e827ca9151acc91f1037c1c330a6df320aa5c5c9e88c60 pmc_33153205.pdf Title: A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome Subject: Rejection-associated gene expression has been characterized in renal allograft biopsies for cause. The aim is to evaluate rejection gene expression in subclinical rejection and in biopsies with borderline changes or interstitial fibrosis and tubular atrophy (IFTA). We included 96 biopsies. Most differentially expressed genes between normal surveillance biopsies (n = 17) and clinical rejection (n = 12) were obtained. A rejection-associated gene (RAG) score was defined as its geometric mean. The following groups were considered: (a) subclinical rejection (REJ-S, n = 6); (b) borderline changes in biopsies for cause (BL-C, n = 13); (c) borderline changes in surveillance biopsies (BL-S, n = 12); (d) IFTA in biopsies for cause (IFTA-C, n = 20); and (e) IFTA in surveillance biopsies (IFTA-S, n = 16). The outcome variable was death-censored graft loss or glomerular filtration rate decline 30 % at 2 years. A RAG score containing 109 genes derived from normal and clinical rejection (area under the curve, AUC = 1) was employed to classify the study groups. A positive RAG score was observed in 83% REJ-S, 38% BL-C, 17% BL-S, 25% IFTA-C, and 5% IFTA-S. A positive RAG score was an independent predictor of graft outcome from histological diagnosis (hazard ratio: 3.5 and 95% confidence interval: 1.1–10.9; p = 0.031). A positive RAG score predicts graft outcome in surveillance and for cause biopsies with a less severe phenotype than clinical rejection. Keywords: renal transplantation; biopsies; rejection; transcriptomics; microarrays; borderline changes; interstitial fibrosis and tubular atrophy Author: Betty Chamoun, Anna Caraben, Irina B. Torres, Joana Sellares, Raquel Jiménez, Néstor Toapanta, Ignacio Cidraque, Alejandra Gabaldon, Manel Perelló, Ricardo Gonzalo, Francisco O’Valle, Francesc Moreso and Daniel Serón Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Wed Nov 4 04:55:59 2020 CET ModDate: Wed Nov 4 06:43:06 2020 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 793514 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HJOMHV+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 KMJAJM+VnURWPalladioL Type 1 Custom yes yes no 15 0 SZRJRZ+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 WNKQDT+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 XKNXPM+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 OFLXAT+Rpxr Type 1 Builtin yes yes no 32 0 UNQNNY+Pxsy Type 1 Builtin yes yes no 36 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 44 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 47 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 69 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 73 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 77 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 93 0 TGMEOR+Rpcxr Type 1 Builtin yes yes no 124 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 128 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:49:02 CEST RepresentationInformation: pmc_33153205.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 11:43:32 CEST Size: 793514 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 312 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Principal Component Analysis Using Gene Transcripts Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Rejection-Associated Gene Score (RAG Score) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: RAG Score and Outcome Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Biopsies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: RNA Extraction and Microarray Hybridization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Statistics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Info: Title: A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome Author: Betty Chamoun, Anna Caraben, Irina B. Torres, Joana Sellares, Raquel Jiménez, Néstor Toapanta, Ignacio Cidraque, Alejandra Gabaldon, Manel Perelló, Ricardo Gonzalo, Francisco O’Valle, Francesc Moreso and Daniel Serón Subject: Rejection-associated gene expression has been characterized in renal allograft biopsies for cause. The aim is to evaluate rejection gene expression in subclinical rejection and in biopsies with borderline changes or interstitial fibrosis and tubular atrophy (IFTA). We included 96 biopsies. Most differentially expressed genes between normal surveillance biopsies (n = 17) and clinical rejection (n = 12) were obtained. A rejection-associated gene (RAG) score was defined as its geometric mean. The following groups were considered: (a) subclinical rejection (REJ-S, n = 6); (b) borderline changes in biopsies for cause (BL-C, n = 13); (c) borderline changes in surveillance biopsies (BL-S, n = 12); (d) IFTA in biopsies for cause (IFTA-C, n = 20); and (e) IFTA in surveillance biopsies (IFTA-S, n = 16). The outcome variable was death-censored graft loss or glomerular filtration rate decline 30 % at 2 years. A RAG score containing 109 genes derived from normal and clinical rejection (area under the curve, AUC = 1) was employed to classify the study groups. A positive RAG score was observed in 83% REJ-S, 38% BL-C, 17% BL-S, 25% IFTA-C, and 5% IFTA-S. A positive RAG score was an independent predictor of graft outcome from histological diagnosis (hazard ratio: 3.5 and 95% confidence interval: 1.1 10.9; p = 0.031). A positive RAG score predicts graft outcome in surveillance and for cause biopsies with a less severe phenotype than clinical rejection. 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