title: Serial peripheral blood perforin and granzyme B gene expression measurements for prediction of acute rejection in kidney graft recipients.
abstract: In the present study we investigated whether peripheral blood gene expression measurements may serve as an early and non-invasive tool to predict renal allograft rejection. Peripheral blood was collected twice weekly after transplantation and gene expression was measured using real-time polymerase chain reaction (PCR). Recipients with acute rejection (n = 17) had higher levels of perforin and granzyme B transcript on days 5-7, 8-10, 11-13, 17-19, 20-22, and 26-29, as compared to patients without rejection (n = 50, p < 0.05 in all cases). Rejection diagnosis using gene expression criteria, determined with receiver operating characteristic (ROC) curves, was possible 2-30 days before traditional diagnosis (median 11 days). The best diagnostic result was obtained from samples taken on days 8-10, with a specificity of 90% and a sensitivity of 82% for perforin, and a specificity of 87% and sensitivity of 72% for granzyme B. Decreases in perforin (p < 0.01) and granzyme B expression (p < 0.05) were observed after initiation of anti-rejection therapy. Our data indicate that gene expression measurement is a useful tool for the recognition of graft rejection in its earliest stages. Serial measurements could be implemented as a monitoring system to highlight patients at higher risk of rejection, making them candidates for biopsy or pre-emptive anti-rejection therapy.
authors.affiliation: Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Simon
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.forename: Manfred
authors.initials: M
authors.lastname: Wiesel
authors.forename: Ralf C
authors.initials: RC
authors.lastname: Ott
authors.forename: Caner
authors.initials: C
authors.lastname: Süsal
mesh_terms: D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis*; D053804:Granzymes; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D054353:Perforin; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D012372:ROC Curve; D012016:Reference Values; D012086:Reoperation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000097:blood / Q000235:genetics*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases