title: A common blood gene assay predates clinical and histological rejection in kidney and heart allografts.
abstract: We assayed our recently defined blood gene panel, diagnostic for kidney and cardiac acute rejection (AR), for its ability to predict biopsy-confirmed renal and cardiac AR prior to clinical or histological AR detection. We utilized a subset of 63 patients from our recent studies with biopsy-confirmed AR (n=40 kidney AR, n=23 cardiacAR) who had paired blood samples collected within 6 months before and after AR. Blood samples were analyzed by quantitative polymerase chain reaction (QPCR) for 10 genes, modeled across differing panels of 5 genes for kidney and heart AR to classify each sample with a quantitative prediction score for rejection. The performance accuracy of the 5-gene panels for AR were compared to the only commercially available QPCR blood assay (AlloMap). A blood gene-based molecular call for AR was made -3 months prior to the histological AR diagnosis in both kidney (92% predicted probability) and cardiac (80% predicted probability) transplant patients and outperformed the AlloMapTM blood test for accuracy and sensitivity [area under the curve (AUC)=0.917 for the kidney 5 genes and 0.915 for the cardiac 5 genes versus an AUC=0.72 for AlloMap]. Serial, posttransplant, targeted profiling of blood samples for a set of 10 genes provides a means to identify kidney and heart transplant recipients at high risk for graft dysfunction and, in the absence of immunosuppression customization, fated to advance to histological rejection and increased graft and patient morbidity.
authors.forename: Minnie
authors.initials: M
authors.lastname: Sarwal
authors.forename: Tara
authors.initials: T
authors.lastname: Sigdel
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002648:Child; D002874:Chromosome Mapping / Q000379:methods; D005820:Genetic Testing; D006084:Graft Rejection / Q000235:genetics* / Q000473:pathology* / Q000517:prevention & control; D016027:Heart Transplantation; D006801:Humans; D016030:Kidney Transplantation; D016133:Polymerase Chain Reaction / Q000379:methods; D012372:ROC Curve; D012680:Sensitivity and Specificity; D059467:Transcriptome / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers