Imperial College London
Alternate

PROFESSOR H. TERENCE COOK

Faculty of Medicine, Department 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{Dominy:2019:10.1016/j.ekir.2018.09.005,
author = {Dominy, KM and Willicombe, M and Al, Johani T and Beckwith, H and Goodall, D and Brookes, P and Cook, HT and McLean, A and Roufosse, CA},
doi = {10.1016/j.ekir.2018.09.005},
journal = {Kidney International Reports},
pages = {148--158},
title = {Molecular assessment of C4d positive renal transplant biopsies without evidence of rejection},
url = {http://dx.doi.org/10.1016/j.ekir.2018.09.005},
volume = {4},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - IntroductionImmunohistochemical staining for C4d in peritubular capillaries has been part of antibody-mediated rejection (AbMR) definition in the Banff Classification for Allograft Pathology since 2003. However, it has limited sensitivity and specificity, therefore the clinical significance of C4d-positive biopsies without evidence of rejection (C4d+ WER) is unknown. We investigated the transcript levels of genes associated with AbMR in C4d+ WER biopsies from both ABO-compatible and incompatible renal transplant patients.MethodsRNA was extracted from formalin-fixed paraffin-embedded renal transplant biopsies (n = 125) and gene expression analysis of 35 AbMR-associated transcripts carried out using the NanoString nCounter system.ResultsAbMR-associated transcripts were significantly increased in samples with AbMR or suspicious AbMR. A subgroup of 17 of 35 transcripts that best distinguished AbMR from C4d-negative biopsies without evidence of rejection was used to study C4d+ WER samples. There was no differential expression between C4d-negative and C4d+ WER from both ABO-incompatible and -compatible transplants. The geometric mean of 17 differentially expressed genes was used to assign the C4d+ WER biopsies a high- or low-AbMR transcript score. Follow-up biopsies showed AbMR within 1 year of initial biopsy in 5 of 7 high-AbMR transcript patients but only 2 of 46 low-AbMR transcript patients. In multivariate logistic regression analysis, elevated transcript levels in a C4d+ WER biopsy were associated with increased odds for biopsy-proven AbMR on follow-up (P = 0.032, odds ratio 16.318), whereas factors including donor-specific antibody (DSA) status and time since transplantation were not.ConclusionGene expression analysis in C4d+ WER samples has the potential to identify patients at higher risk of developing AbMR.
AU  - Dominy,KM
AU  - Willicombe,M
AU  - Al,Johani T
AU  - Beckwith,H
AU  - Goodall,D
AU  - Brookes,P
AU  - Cook,HT
AU  - McLean,A
AU  - Roufosse,CA
DO  - 10.1016/j.ekir.2018.09.005
EP  - 158
PY  - 2019///
SN  - 2468-0249
SP  - 148
TI  - Molecular assessment of C4d positive renal transplant biopsies without evidence of rejection
T2  - Kidney International Reports
UR  - http://dx.doi.org/10.1016/j.ekir.2018.09.005
UR  - http://hdl.handle.net/10044/1/64641
VL  - 4
ER  -
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