Imperial College London

PROFESSOR H. TERENCE COOK

Faculty of MedicineDepartment of Immunology and Inflammation

Emeritus Professor
 
 
 
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Contact

 

+44 (0)20 3313 2009t.h.cook

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N9Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Roufosse:2022:ndt/gfab231,
author = {Roufosse, C and Cook, H and Dominy, K and Willicombe, M and Beadle, J and Szydlo, R and McLean, A and Toulza, F},
doi = {ndt/gfab231},
journal = {Nephrology Dialysis Transplantation},
pages = {1576--1584},
title = {Diagnostic application of transcripts associated with antibody-mediated rejection in kidney transplant biopsies},
url = {http://dx.doi.org/10.1093/ndt/gfab231},
volume = {37},
year = {2022}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BackgroundThe diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of “Increased Expression Of Thoroughly Validated Gene Transcripts/Classifiers Strongly Associated With AMR” as a diagnostic criteria.MethodWe used qRT-PCR for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27); biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts (AMRsusp, n = 49) and biopsies that would never meet criteria for AMR (No-AMR, n = 221).ResultsA 10-gene AMR score trained by a receiver-operating characteristic to identify AMR found 16 cases with a high score amongst the AMRsusp cases (AMRsusp-high) that had significantly worse graft survival than those with a low score (AMRsusp-low) (n = 33). In both univariate and multivariate Cox regression analysis, the AMR 10-gene score was significantly associated with an increased hazard ratio for graft loss in the AMRsusp group (HR 1.109, p = 0.004 and HR 1.138, p = 0.012), but not in the whole cohort. Net reclassification index and integrated discrimination improvement analyses demonstrated improved risk classification and superior discrimination respectively for graft loss when considering the gene score in addition to histological and serological data, but only in the AMRsusp group, not the whole cohort.ConclusionsThis study provides evidence that a gene score strongly associated with AMR helps identify cases at higher risk of graft loss in biopsies that are suspicious for AMR but don’t meet full criteria.
AU - Roufosse,C
AU - Cook,H
AU - Dominy,K
AU - Willicombe,M
AU - Beadle,J
AU - Szydlo,R
AU - McLean,A
AU - Toulza,F
DO - ndt/gfab231
EP - 1584
PY - 2022///
SN - 0931-0509
SP - 1576
TI - Diagnostic application of transcripts associated with antibody-mediated rejection in kidney transplant biopsies
T2 - Nephrology Dialysis Transplantation
UR - http://dx.doi.org/10.1093/ndt/gfab231
UR - https://academic.oup.com/ndt/article/37/8/1576/6329647
UR - http://hdl.handle.net/10044/1/90670
VL - 37
ER -