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| Status |
Public on Apr 01, 2013 |
| Title |
GENOMICS TO IDENTIFY HLA IDENTICAL RENAL TRANSPLANT TOLERANCE SIGNATURES |
| Organism |
Homo sapiens |
| Experiment type |
Third-party reanalysis
Expression profiling by array
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| Summary |
Immunosuppression is needed in HLA identical sibling renal transplantation. We conducted a tolerance trial in this patient cohort using Alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, planning complete drug withdrawal by 24 months post-transplantation. After an additional 12 months with no immunosuppression, normal biopsies and renal function, recipients were considered tolerant. Twenty recipients were enrolled. Of the first 10 (>36 months post-transplantation), 5 had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence and 3 had subclinical rejection in protocol biopsies (non-tolerant). Microchimerism disappeared after 1 year, and CD4+CD25highCD127-FOXP3+ T cells and CD19+IgD/M+CD27- B cells increased to 5 years post-transplantation in both groups, whereas immune/inflammatory gene expression pathways in the peripheral blood and urine were differentially downregulated in tolerant compared to non-tolerant recipients. Therefore, in this HLA identical renal transplant tolerance trial, absent chimerism, Treg and Breg immunophenotypes were indistinguishable between tolerant and non-tolerant recipients, but global genomic changes indicating immunomodulation were observed only in tolerant recipients.
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| Overall design |
A total of 46 PBMC samples representing blood draws from four time points in the first 9 recipients were processed for microarray analysis (The Scripps Research Institute, La Jolla, CA). The analyzed time points were: immediately pre-operatively in the absence of immunosuppression (n=9); post-operatively at 1 year (n=8, range 11-13 months); at 2 years (n=12, range 18-25 months); >3 years (n=17, range 32-48 months). (At year 2 and at > 3 years, repeated samples were obtained from individual subjects, and at one year, one subject had a technically unsatisfactory sample.) To discount the effects of immunosuppression on gene expression, microarray data were included on whole blood from 18 healthy human subjects (controls: GSE40586; NCBI Gene Expression Omnibus [GEO] repository).
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| Contributor(s) |
Kurian SM |
| Citation(s) |
23787913 |
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| Submission date |
Mar 28, 2013 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Sunil Kurian |
| E-mail(s) |
smkurian@scripps.edu
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| Phone |
858-784-7759
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| Organization name |
The Scripps Research Institute
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| Department |
Molecular and Experimental Medicine
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| Street address |
10550 N Torrey Pines Road
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (2) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (46)
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| Relations |
| Reanalysis of |
GSM997333 |
| Reanalysis of |
GSM997343 |
| Reanalysis of |
GSM997345 |
| Reanalysis of |
GSM997347 |
| Reanalysis of |
GSM997358 |
| Reanalysis of |
GSM997361 |
| Reanalysis of |
GSM997363 |
| Reanalysis of |
GSM997342 |
| Reanalysis of |
GSM997351 |
| Reanalysis of |
GSM997341 |
| Reanalysis of |
GSM997369 |
| Reanalysis of |
GSM997370 |
| Reanalysis of |
GSM997368 |
| Reanalysis of |
GSM997337 |
| Reanalysis of |
GSM997360 |
| Reanalysis of |
GSM997366 |
| Reanalysis of |
GSM997338 |
| Reanalysis of |
GSM997334 |
| BioProject |
PRJNA194628 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45593_RAW.tar |
185.6 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE45593_log2_RMA_all_samples.txt.gz |
7.0 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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