Detection of Cardiac Allograft Rejection and Response to Immunosuppressive Therapy With Peripheral Blood Gene Expression

Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Circulation (Impact Factor: 14.43). 01/2005; 110(25):3815-21. DOI: 10.1161/01.CIR.0000150539.72783.BF
Source: PubMed


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.
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).
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.

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    • "Peripheral blood monitoring of AR in heart transplant patients has also been evaluated. Horwitz et al. identified a gene expression profile that identified AR from control samples [34]. Interestingly, an analysis of expression profiles following treatment for AR showed an intermediate level of expression for most genes suggesting the persistence of low-level inflammation/immunity. "
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    • "A simple blood test that predicts the extent of coronary artery disease could provide an additional useful tool for screening for coronary artery disease in at-risk populations. A similar approach has been successfully used for detection of cardiac allograft rejection and the response to immunosuppressive therapy [23]. "
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