Measurement of protective genes in allograft rejection
| Title: | Measurement of protective genes in allograft rejection |
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| Patent Number: | 6,900,015 |
| Publication Date: | May 31, 2005 |
| Appl. No: | 09/777732 |
| Application Filed: | February 06, 2001 |
| Abstract: | The invention relates to methods of evaluating transplant rejection in a host comprising determining a heightened magnitude of gene expression of genes in rejection-associated gene clusters. The disclosed gene clusters include genes that are substantially co-expressed with cytotoxic lymphocyte pro-apoptotic genes, cytoprotective genes and several other cytokine and immune cell genes. |
| Inventors: | Avihingsanon, Yingyos (Boston, MA, US); Ma, Nali (Wirchester, MA, US); Strom, Terry B. (Brookline, MA, US); Soares, Miguel C. (Boston, MA, US); Ferran, Christiane (Brookline, MA, US); Suthanthiran, Manikkam (Scarsdale, NY, US) |
| Assignees: | Beth Israel Deaconess Medical Center, Inc. (Boston, MA, US), Cornell Research Foundation, Inc. (Ithaca, NY, US) |
| Claim: | 1. A method for monitoring the status of a transplanted organ in a host, the method comprising: a) providing a post-transplantation sample from the host; b) determining the level of gene expression in the post-transplantation sample of at least one gene, wherein the at least one gene is heme oxygenase 1 (HO1) or A20; c) comparing the level of gene expression of the at least one gene in the post-transplantation sample to a baseline level of gene expression of the at least one gene or to a baseline level of gene expression of a constitutively expressed gene; and d) determining whether the at least one gene is upregulated relative to the baseline level of gene expression of the at least one gene or to the baseline level of gene expression of a constituitively expressed gene, wherein upregulation of the at least one gene indicates that the host is likely to experience transplant rejection; thereby monitoring the status of the transplanted organ. |
| Claim: | 2. The method of claim 1 , wherein the post-transplantation sample is a graft biopsy. |
| Claim: | 3. The method of claim 1 , wherein the post-transplantation sample is a fluid test sample. |
| Claim: | 4. The method of claim 3 , wherein the fluid test sample is selected from the group consisting of: urine, peripheral blood, bile, bronchoalveolar lavage fluid, pericardial fluid, gastrointestinal juice, feces, and fluid gathered from an anatomic area in proximity to an allograft. |
| Claim: | 5. The method of claim 1 , wherein determining the level of gene expression comprises determining the level of expression of HO1 and A20. |
| Claim: | 6. The method of claim 1 , wherein the transplant rejection is an acute rejection. |
| Claim: | 7. The method of claim 6 , wherein the acute rejection is an early acute rejection. |
| Claim: | 8. The method of claim 1 , wherein the transplant rejection is chronic transplant rejection. |
| Claim: | 9. The method of claim 8 , wherein the at least one gene is A20 and wherein upregulation of A20 indicates that the host is likely to experience chronic transplant rejection. |
| Claim: | 10. The method of claim 9 , further comprising determining the level of gene expression of HO1, wherein a low expression level of HO1 indicates that the host is likely to experience chronic transplant rejection. |
| Claim: | 11. The method of claim 1 , wherein the host is a human patient. |
| Claim: | 12. The method of claim 1 , wherein the transplanted organ is a kidney. |
| Claim: | 13. The method of claim 1 , wherein the sample is obtained during the non-rejection period. |
| Claim: | 14. The method of claim 1 , wherein the constitutively expressed gene is glyceraldehyde-3-phosphate dehydrogenase. |
| Claim: | 15. The method of claim 1 , wherein the constitutively expressed gene is cyclophilin B or actin. |
| Claim: | 16. The method of claim 1 , wherein the at least one gene is HO1. |
| Claim: | 17. The method of claim 1 , wherein the at least one gene is A20. |
| Current U.S. Class: | 435/6 |
| Patent References Cited: | 5213961 May 1993 Bunn et al. 5569588 October 1996 Ashby et al. 6187534 February 2001 Strom et al. |
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| Assistant Examiner: | Tung, Joyce |
| Primary Examiner: | Horlick, Kenneth R. |
| Attorney, Agent or Firm: | Fish & Richardson P.C. |
| Accession Number: | edspgr.06900015 |
| Database: | USPTO Patent Grants |
| Language: | English |
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