A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome
Chamoun, Betty (Hospital Universitari Vall d'Hebron)
Caraben, Anna (Hospital Universitari Vall d'Hebron)
Torres, Irina B. (Hospital Universitari Vall d'Hebron)
Sellares, Joana (Hospital Universitari Vall d'Hebron)
Jiménez, Raquel (Hospital Universitari Vall d'Hebron)
Toapanta, Néstor (Hospital Universitari Vall d'Hebron)
Cidraque, Ignacio (Hospital Universitari Vall d'Hebron)
Gabaldón, Alejandra (Hospital Universitari Vall d'Hebron)
Perelló, Manel (Hospital Universitari Vall d'Hebron)
Gonzalo Sanz, Ricardo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
O'Valle, Francisco (Pathology Department, Instituto de Biopatología y Medicina Regenerativa (IBIMER), Instituto de Investigación Biosanitaria (ibs.GRANADA), University of Granada, 18010 Granada, Spain)
Moreso, Francesc (Universitat Autònoma de Barcelona. Departament de Medicina)
Seron, Daniel (Universitat Autònoma de Barcelona. Departament de Medicina)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	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 rejectio.
Ajuts:	Ministerio de Ciencia e Innovación PI11/02081 Ministerio de Ciencia e Innovación PI11/02345 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017 SGR 1342
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Renal transplantation ; Biopsies ; Rejection ; Transcriptomics ; Microarrays ; Borderline changes ; Interstitial fibrosis and tubular atrophy
Publicat a:	International journal of molecular sciences, Vol. 21 (november 2020) , ISSN 1422-0067

DOI: 10.3390/ijms21218237
PMID: 33153205

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