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E-GEOD-5967 - Transcription profiling of human peripheral blood to detect cardiac allograft rejection and response to immunosuppressive therapy

Status
Submitted on 4 October 2006, released on 14 June 2008, last updated on 27 March 2012
Organism
Homo sapiens
Samples (21)
Array (1)
Protocols (6)
Description
BACKGROUND: Assessment of gene expression in peripheral blood may provide a noninvasive screening test for allograft rejection. We hypothesized that changes in peripheral blood expression profiles would correlate with biopsy-proven rejection and would resolve after treatment of rejection episodes. METHODS AND RESULTS: We performed a case-control study nested within a cohort of 189 cardiac transplant patients who had blood samples obtained during endomyocardial biopsy (EMB). Using Affymetrix HU133A microarrays, we analyzed whole-blood expression profiles from 3 groups: (1) control samples with negative EMB (n=7); (2) samples obtained during rejection (at least International Society for Heart and Lung Transplantation grade 3A; n=7); and (3) samples obtained after rejection, after treatment and normalization of the EMB (n=7). We identified 91 transcripts differentially expressed in rejection compared with control (false discovery rate <0.10). In postrejection samples, 98% of transcripts returned toward control levels, displaying an intermediate expression profile for patients with treated rejection (P<0.0001). Cluster analysis of the 40 transcripts with >25% change in expression levels during rejection demonstrated good discrimination between control and rejection samples and verified the intermediate expression profile of postrejection samples. Quantitative real-time polymerase chain reaction confirmed significant differential expression for the predictive markers CFLAR and SOD2 (UniGene ID No. 355724 and No. 384944). CONCLUSIONS: These data demonstrate that peripheral blood expression profiles correlate with biopsy-proven allograft rejection. Intermediate expression profiles of treated rejection suggest persistent immune activation despite normalization of the EMB. If validated in larger studies, expression profiling may prove to be a more sensitive screening test for allograft rejection than EMB. Experiment Overall Design: Case- control study with three groups. Patients with rejection (r1-r7), follow-up samples after treatment of rejection (post1-7), and controls with no rejection (con1-7)
Experiment types
transcription profiling by array, unknown experiment type
Contact
Citation
Detection of cardiac allograft rejection and response to immunosuppressive therapy with peripheral blood gene expression. Phillip A Horwitz, Emily J Tsai, Mary E Putt, Joan M Gilmore, John J Lepore, Michael S Parmacek, Andrew C Kao, Shashank S Desai, Lee R Goldberg, Susan C Brozena, Mariell L Jessup, Jonathan A Epstein, Thomas P Cappola. Circulation 110(25):3815-21 (2004)
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-5967.idf.txt
Sample and data relationshipE-GEOD-5967.sdrf.txt
Raw data (1)E-GEOD-5967.raw.1.zip
Processed data (1)E-GEOD-5967.processed.1.zip
Array designA-AFFY-33.adf.txt
R ExpressionSetE-GEOD-5967.eSet.r
Links