A Computational Gene Expression Score for Predicting Immune Injury in Renal Allografts

Whole genome microarray meta-analyses of 1030 kidney, heart, lung and liver allograft biopsies identified a common immune response module (CRM) of 11 genes that define acute rejection (AR) across different engrafted tissues. We evaluated if the CRM genes can provide a molecular microscope to quantif...

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Bibliographic Details
Published in:PloS one 2015-09, Vol.10 (9), p.e0138133-e0138133
Main Authors: Sigdel, Tara K, Bestard, Oriol, Tran, Tim Q, Hsieh, Szu-Chuan, Roedder, Silke, Damm, Izabella, Vincenti, Flavio, Sarwal, Minnie M
Format: Article
Language:English
Subjects:
Acute Kidney Injury - immunology
Adolescent
Adult
Allografts
Atrophy
Biomarkers
Biopsy
CD6 antigen
Child
Computation
Computer applications
Computer Simulation
Customer relationship management software
CXCL10 protein
Data mining
Data processing
Demographic variables
Demographics
Demography
DNA microarrays
Female
Fibrosis
Gene expression
Gene Expression Regulation
Genes
Genomes
Genomics
Graft rejection
Graft Rejection - immunology
Grafting
Histology
Homografts
Humans
Immune response
Immune system
Injuries
Injury analysis
Kidney Transplantation
Kidneys
Lck protein
Life assessment
Liver
Liver transplantation
Male
Mathematical models
Models, Immunological
Nephrology
Patients
Pediatrics
Proteomics
Rejection
Runx3 protein
Surgeons
Surgery
Transplants & implants
Urine
Xenografts
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Summary:Whole genome microarray meta-analyses of 1030 kidney, heart, lung and liver allograft biopsies identified a common immune response module (CRM) of 11 genes that define acute rejection (AR) across different engrafted tissues. We evaluated if the CRM genes can provide a molecular microscope to quantify graft injury in acute rejection (AR) and predict risk of progressive interstitial fibrosis and tubular atrophy (IFTA) in histologically normal kidney biopsies. Computational modeling was done on tissue qPCR based gene expression measurements for the 11 CRM genes in 146 independent renal allografts from 122 unique patients with AR (n = 54) and no-AR (n = 92). 24 demographically matched patients with no-AR had 6 and 24 month paired protocol biopsies; all had histologically normal 6 month biopsies, and 12 had evidence of progressive IFTA (pIFTA) on their 24 month biopsies. Results were correlated with demographic, clinical and pathology variables. The 11 gene qPCR based tissue CRM score (tCRM) was significantly increased in AR (5.68 ± 0.91) when compared to STA (1.29 ± 0.28; p < 0.001) and pIFTA (7.94 ± 2.278 versus 2.28 ± 0.66; p = 0.04), with greatest significance for CXCL9 and CXCL10 in AR (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0138133