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| Status |
Public on Oct 04, 2006 |
| Title |
Detection of cardiac allograft rejection and response to immunosuppressive therapy with peripheral blood gene expression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
Keywords: human, peripheral blood, before and after therpay, untreated control
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| 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)
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| Contributor(s) |
Cappola TP, Horwitz PA, Epstein JA, Tsai EJ, Putt ME |
| Citation(s) |
15583081 |
| Submission date |
Oct 04, 2006 |
| Last update date |
Aug 10, 2018 |
| Contact name |
Thomas Cappola |
| E-mail(s) |
thomas.cappola@uphs.upenn.edu
|
| Organization name |
Univeristy of Pennsylvania School of Medicine
|
| Department |
Penn Cardiovascular Institute
|
| Street address |
6 Penn Tower, 3400 Spruce Street
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
|
| Samples (21)
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| GSM138600 |
patient with rejection r4 |
| GSM138601 |
patient with rejection r5 |
| GSM138602 |
patient with rejection r6 |
| GSM138603 |
patient with rejection r7 |
| GSM138604 |
follow-up sample after treatment of rejection post1 |
| GSM138605 |
follow-up sample after treatment of rejection post2 |
| GSM138606 |
follow-up sample after treatment of rejection post3 |
| GSM138607 |
follow-up sample after treatment of rejection post4 |
| GSM138608 |
follow-up sample after treatment of rejection post5 |
| GSM138609 |
follow-up sample after treatment of rejection post6 |
| GSM138610 |
follow-up sample after treatment of rejection post7 |
| GSM138611 |
control with no rejection con1 |
| GSM138612 |
control with no rejection con2 |
| GSM138613 |
control with no rejection con3 |
| GSM138614 |
control with no rejection con4 |
| GSM138615 |
control with no rejection con5 |
| GSM138616 |
control with no rejection con6 |
| GSM138617 |
control with no rejection con7 |
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| Relations |
| BioProject |
PRJNA97435 |
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