Methods and Compositions for Determining a Graft Tolerant Phenotype in a Subject

Abstract

Methods are provided for determining whether a subject has a graft tolerant phenotype. In practicing the subject methods, the expression of at least 5 genes in a sample from the subject, e.g., a blood sample, is assayed to obtain a gene expression result for the at least 5 genes. The obtained gene expression result for the at least 5 genes is then employed to determine whether the subject has a graft tolerant phenotype. 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, including the determination of an immunosuppressive therapy regimen.

1 . A method of determining whether a subject who has received an allograft has a graft tolerant phenotype, said method comprising:
 (a) evaluating the level of expression of at least 5 genes in a sample from said subject to obtain a gene expression result, wherein said at least 5 genes are selected from either Table 2 or Table 4; and   (b) determining whether said subject has a graft tolerant phenotype based on said gene expression result.   
     
     
         2 . The method according to  claim 1 , wherein said allograft is a renal allograft. 
     
     
         3 . The method according to  claim 1 , wherein said sample is a blood sample. 
     
     
         4 . The method according to  claim 1 , wherein said evaluating step comprises assaying said sample for an expression product of said at least 5 genes. 
     
     
         5 . The method according to  claim 4 , wherein said expression product is selected from one both of: a nucleic acid transcript and a protein. 
     
     
         6 . The method of  claim 5 , wherein said expression product is a nucleic acid transcript and said evaluating step comprises performing one or more of the following: a RT-PCR assay, a microarray assay, and a Northern blot. 
     
     
         7 . The method according to  claim 1 , wherein the expression level of at least 10 genes from either Table 2 or Table 4 is evaluated. 
     
     
         8 . The method according to  claim 1 , wherein the expression level of all of the genes from either Table 2 or Table 4 is evaluated. 
     
     
         9 . The method according to  claim 1 , wherein said determining step comprises comparing said gene expression result to a reference gene expression profile. 
     
     
         10 . The method according to  claim 9 , wherein said reference gene expression profile is selected from: a graft tolerant phenotype gene expression profile and a graft intolerant phenotype gene expression profile. 
     
     
         11 . A method of managing immunosuppressive therapy treatment in a subject having an allograft, said method comprising:
 (a) determining whether said subject has a graft tolerant phenotype according to  claim 1 ; and   (b) managing future immunosuppressive therapy treatment in said subject based on said determining step (a).   
     
     
         12 . A system for determining whether a subject who has received an allograft has a graft tolerant phenotype, said system comprising:
 (a) a gene expression evaluation element for evaluating the level of expression of at least 5 genes in a sample from said subject to obtain a gene expression result, wherein said at least 5 genes are selected from either Table 2 or Table 4; and   (b) a graft tolerance determination element for employing said gene expression result to determining whether said subject has a graft tolerant phenotype.   
     
     
         13 . The system according to  claim 12 , wherein said gene expression evaluation element comprises at least one reagent for assaying a sample for an expression product of said at least 5 genes. 
     
     
         14 . The system according to  claim 12 , wherein said expression product of said at least one gene is selected from: a nucleic acid transcript and a protein. 
     
     
         15 . The system according to  claim 12 , wherein the expression level all of the genes in either Table 2 or Table 4 is assessed. 
     
     
         16 . A kit for determining whether a subject who has received an allograft has a graft tolerant phenotype, said kit comprising:
 (a) a gene expression evaluation element for evaluating the level of expression of at least 5 genes in a sample from said subject to obtain a gene expression result, wherein said at least 5 genes are selected from either Table 2 or Table 4; and   (b) a phenotype determination element for employing said gene expression result to determine whether said subject has a graft tolerant phenotype.   
     
     
         17 . The kit according to  claim 16 , wherein said gene expression evaluation element comprises at least one reagent for evaluating a sample for an expression product of said gene. 
     
     
         18 . The kit according to  claim 17 , wherein said expression product of said at least one gene is selected from: a nucleic acid transcript and a protein. 
     
     
         19 . The kit according to  claim 17 , wherein the expression level all of the genes in either Table 2 or Table 4 is assessed. 
     
     
         20 . A computer program product for determining whether a subject who has undergone a renal allograft has a graft tolerant phenotype, wherein said computer program product, when loaded onto a computer, is configured to employ a gene expression result from a sample derived from said subject to determining whether a subject who has undergone a renal allograft has a graft tolerant phenotype, wherein said gene expression result comprises expression data for at least one gene from Table 2 or Table 4.