Functional Genomic Analysis of Peripheral Blood During Early Acute Renal Allograft Rejection

• DOI: 10.1097/tp.0b013e3181b7ccc6
• Publication Date: 2009-10-02T07:15:01Z
• Authors: Oliver P. Günther; Robert F. Balshaw; Andreas Scherer; Zsuzsanna Hollander; Alice Mui; Timothy J. Triche; Gabriela Cohen Freue; Guiyun Li; Raymond T. Ng; Janet Wilson-McManus; W Robert McMaster; Bruce M. McManus; Paul A. Keown
• Keywords: Graft Rejection; 0303 health sciences; DNA, Complementary; Time Factors; Biopsy; Gene Expression Profiling; Recombinant Fusion Proteins; Antibodies, Monoclonal; Discriminant Analysis; Reproducibility of Results; Genomics; Kidney Transplantation; 3. Good health; Basiliximab; 03 medical and health sciences; Phenotype; Case-Control Studies; Acute Disease; Humans; RNA; Prospective Studies; Immunosuppressive Agents; Follow-Up Studies

Acute graft rejection is an important clinical problem in renal transplantation and adverse predictor for long-term survival. Peripheral blood biomarkers that provide evidence of early may offer option posttransplant monitoring, optimize the utility biopsy, permit timely effective therapeutic intervention to minimize damage.In this feasibility study (n=58), we have used gene expression profiling a case-control design compare whole samples between normal subjects (n=20) patients with (n=11) or without (n=22) biopsy-confirmed acute (BCAR) borderline changes (n=5).A total 183 probe sets representing 160 genes were differentially expressed (false discovery rate [FDR] <0.01) BCAR, from which linear discriminant analysis cross-validation identified initial signature 24 sets, more refined set 11 found classify subject correctly. Cross-validation suggested out-of-sample sensitivity 73% specificity 91% identification BCAR. An increase classifier correlated closely during first 3 months posttransplant. Biological evaluation indicated encompassed processes related immune response, signal transduction, cytoskeletal reorganization.Preliminary indicates peripheral yield relevant measure occurrence BCAR potential tool immunologic monitoring. These results now require confirmation larger cohort.