Methods and compositions for evaluating graft survival in a solid organ transplant recipient

Abstract

Methods are provided for evaluating a subject for graft survival, e.g., in terms of predicting graft survival, identifying the presence of a deleterious graft condition, such as CAN and DT, identifying the severity and class of acute rejection, etc, in a subject are provided. In practicing the subject methods, the expression of at least one gene in a sample from the subject, e.g., a blood or biopsy sample, is assayed, e.g., at the nucleic acid and/or protein level, to evaluate the subject. Also provided are compositions, systems and kits that find use in practicing the subject methods. The methods and compositions find use in a variety of applications.

What is claimed is: 
     
       1. A method of evaluating graft survival in a subject, said method comprising:
 assessing expression of at least two genes in a sample from said subject to evaluate graft survival in said subject, wherein said at least two genes comprises HIST1H2B and IGHG3.   
     
     
       2. The method according to  claim 1 , wherein said expression of at least two genes is assessed by assaying said sample for a nucleic acid transcript of said gene. 
     
     
       3. The method according to  claim 1 , wherein said expression of at least two genes is assessed by assaying said sample for an expression product of said gene. 
     
     
       4. The method according to any of  claim 1 , wherein said sample is a blood sample. 
     
     
       5. The method according to  claim 4 , wherein said blood sample is a peripheral blood sample. 
     
     
       6. The method according to  claim 1 , wherein said sample is a tissue biopsy sample. 
     
     
       7. A method according to  claim 1 , wherein the method comprises: obtaining an expression profile for a sample from said subject. 
     
     
       8. The method according to  claim 7 , wherein said expression profile is compared to a reference expression profile. 
     
     
       9. The method according to  claim 8 , wherein said expression profile is a nucleic acid expression profile. 
     
     
       10. The method according to  claim 8 , wherein said expression profile comprises expression measurements for at least 5 different genes. 
     
     
       11. The method according to  claim 8 , wherein said expression profile is determined using a microarray. 
     
     
       12. The method according to  claim 11 , wherein said microarray is a genomic array. 
     
     
       13. A method of managing post-transplantation therapy in a subject, said method comprising:
 (a) evaluating graft survival in said subject by a method according to  claims 1 ; and   (b) determining a post-transplantation therapy protocol based on said evaluation step (a);   to manage post-transplantation therapy in said subject.   
     
     
       14. The method according to  claim 13 , wherein said subject is a human. 
     
     
       15. The method according to  claim 1 , wherein said at least two genes further comprises one or more genes selected from: AHSA2, TNFRSF10D, MAPK9, IFNAR2, TM4SF9, MIF, SCYE1, MAPK1, TGFBR3, IGKC, IL1R2 and IGL. 
     
     
       16. A method of treating a transplant recipient comprising the steps of:
 (a) determining that the transplant recipient has a graft survival phenotype by evaluating results previously obtained from a quantitative determination of nucleic acid expression levels of at least three genes in a sample from said transplant recipient; and
 treating said transplant recipient by maintaining a current therapeutic regimen; or 
   (b) determining that the transplant recipient has a graft loss phenotype by evaluating results previously obtained from a quantitative determination of the nucleic acid expression levels of at least three genes in a sample from said transplant recipient; and
 treating said transplant recipient by increasing or decreasing a therapeutic regimen; 
   wherein, said evaluating comprises comparing said results to a reference nucleic acid expression profile comprising said at least three genes, and   wherein said at least three genes are selected from the group consisting of GZMK, DUSP1, IFNGR1, MAPK9, EPOR, FOXP3, IL7R, NKTR, ACTB, GBP1, IL7, ISG20, NFE2, PSMB9, STAT3 and TNFRSF1A.   
     
     
       17. The method according to claim 16, wherein said at least three genes comprises GZMK, NKTR, and EPOR. 
     
     
       18. The method according to claim 16, wherein said sample is a blood sample. 
     
     
       19. The method according to claim 16, wherein said blood sample is a peripheral blood sample. 
     
     
       20. The method according to claim 16, wherein said sample is a tissue biopsy sample. 
     
     
       21. The method according to claim 16, wherein said reference nucleic acid expression profile is predictive of a graft loss or graft survival phenotype. 
     
     
       22. The method according to claim 16, wherein said at least three genes is at least 5 genes. 
     
     
       23. The method according to claim 22, wherein said quantitative determination was performed using a microarray. 
     
     
       24. The method according to claim 23, wherein said microarray is a genomic array. 
     
     
       25. The method according to claim 16, wherein said at least three genes comprises DUSP1, IFNGR1, and NKTR. 
     
     
       26. The method according to claim 16, wherein said at least three genes comprises EPOR, CEACAM4, and MAPK9. 
     
     
       27. The method according to claim 16, wherein said at least three genes are selected from the group consisting of: GZMK, NKTR, EPOR, IFNGR1, DUSP1, and MAPK9. 
     
     
       28. The method according to claim 16, comprising: determining that the transplant recipient has a graft loss phenotype that is calcineurin-inhibitor drug nephrotoxicity (DT); and decreasing an immunosuppressive therapy. 
     
     
       29. The method according to claim 16, comprising: (i) determining that the transplant recipient has a graft loss phenotype that is chronic allograft nephropathy (CAN); and (ii) increasing an immunosuppressive therapy, or changing an immunosuppressive therapy by administering a different immunosuppressive drug.