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| Status |
Public on Dec 15, 2012 |
| Title |
Inducing and Predicting Immune Tolerance After Kidney Transplantation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Background
Immune tolerance and persistent mixed chimerism can be achieved reproducibly after combined organ and hematopoietic cell transplantation in mice conditioned with total lymphoid irradiation plus anti-thymocyte globulin. We studied the safety and reproducibility of this approach in a cohort of kidney transplant patients, and tried to identify immune monitoring procedures that can predict tolerance and guide complete immunosuppressive drug withdrawal.
Methods
Ten patients conditioned with 10 doses of total lymphoid irradiation and 5 doses of anti-thymocyte globulin were given kidney transplants and an injection of CD34+ hematopoietic progenitor cells and T cells from HLA matched donors. Blood cell monitoring included changes in chimerism, balance of T cell subsets, gene expression, and responses to donor alloantigens.
Results
Nine of 10 patients developed multi-lineage chimerism without graft versus host disease (GVHD), and all had excellent graft function at the last observation point. Five of these with chimerism persisting for at least 12 months were completely withdrawn from immunosuppressive drugs for 6 to 35 months. Blood cells from patients off drugs showed development of specific unresponsiveness to donor alloantigens, “tolerance” profiles on gene microarrays, early high ratios of regulatory versus conventional naïve T cells, and early high levels of chimerism among NK cells.
Conclusions
Total lymphoid irradiation, and anti-thymocyte globulin promoted the development of persistent chimerism and tolerance in a cohort of patients given kidney transplants and donor cell injections. Assays were identified that can assist in the safe withdrawal of immunosuppressive drugs.
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| Overall design |
45 Agilent Microarray samples were conducted, including 16 tolerance patients, 10 chronic rejection patients, 5 healthy normal controls, and 7 paired pre and post-transplant induced tolerance patients. The aim is to see whether induced tolerance patients show operational tolerance gene expression signature and can withdraw or minimize the immunosuppression regimens.
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| Contributor(s) |
Scandling JD, Busque S, Dejbakhsh-Jones S, Li L, Benike C, Hsieh S, Sigdel T, Mukhopadhyay A, Holmes T, Shizuru JA, Lowsky R, Engleman EG, Sarwal MM, Strober S |
| Citation missing |
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| Submission date |
Jul 13, 2009 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Li Li |
| E-mail(s) |
li.li@mssm.edu
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| Phone |
6507243765
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| Organization name |
Stanford University
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| Department |
Pediatric
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| Lab |
Sarwal Lab
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| Street address |
300 pastuer dr.,
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (45)
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| Relations |
| BioProject |
PRJNA119777 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE17068_RAW.tar |
633.9 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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