Gene expression profiles associated with chronic allograft nephropathy

Abstract

By a genome-wide gene analysis of expression profiles of over 50,000 known or putative gene sequences in peripheral blood, the present inventors have identified a consensus set of gene expression-based molecular biomarkers associated with chronic allograft nephropathy and/or interstitial fibrosis and tubular atrophy CAN/IFTA and subtypes thereof. These genes sets are useful for diagnosis, prognosis, monitoring and/or subtyping of CAN/IFTA.

What is claimed is: 
     
         1 . A method of prognosing, diagnosing or monitoring CAN/IFTA (chronic allograft nephropathy, interstitial fibrosis and tubular atrophy, or chronic allograft nephropathy and interstitial fibrosis and tubular atrophy), comprising
 (a) determining expression levels in a subject of at least 5 genes selected from the genes in Table A, B, C, D, E, F, G, H, I and/or J; and   (b) prognosing, diagnosing or monitoring CAN/IFTA in a subject from the expression levels.   
     
     
         2 . The method of  claim 1 , wherein for each of the at least five genes, step (b) comprises comparing the expression level of the gene in the subject to one or more reference expression levels of the gene associated with CAN/IFTA or lack of CAN/IFTA. 
     
     
         3 . The method of  claim 2 , wherein step (b) further comprises for each of the at least five genes assigning the expression level of the gene in the subject a value or other designation providing an indication whether the subject has or is at risk of CAN/IFTA. 
     
     
         4 . The method of  claim 3 , wherein the expression level of each of the at least five genes is assigned a value on a normalized scale of values associated with a range of expression levels in kidney transplant patients with and without CAN/IFTA. 
     
     
         5 . The method of  claim 3 , wherein the expression level of each of the at least five genes is assigned a value or other designation providing an indication that the subject has is at risk of CAN/IFTA, lacks and is not at risk of CAN/IFTA, or that the expression level is uninformative. 
     
     
         6 . The method of  claim 3 , wherein step (b) further comprises, combining the values or designations for each of the genes to provide a combined value or designation providing an indication whether the subject has or is at risk of CAN/IFTA. 
     
     
         7 . The method of  claim 6 , wherein the method is repeated at different times on the subject. 
     
     
         8 . The method of  claim 1 , wherein the subject has undergone a kidney transplant within 1-10 years of performing step (a). 
     
     
         9 . The method of  claim 1 , wherein step (a) is performed on a blood sample of the subject. 
     
     
         10 . The method of  claim 9 , wherein the blood sample is a peripheral blood sample or a blood plasma sample. 
     
     
         11 . The method of  claim 10 , wherein the peripheral blood sample is a peripheral blood lymphocyte sample. 
     
     
         12 . The method of  claim 1 , wherein the expression levels are determined at the mRNA level or the protein level. 
     
     
         13 . The method of  claim 1 , wherein the determining the expression levels in the subject comprises one or more of the following: (a) hybridizing expression products to an array; (b) nucleic acid amplification; (c) monitoring the formation of an amplification product; or (d) synthesizing a nucleic acid using mRNA as a template. 
     
     
         14 . The method of  claim 1 , wherein the subject is receiving a treatment regimen prior to the prognosing, diagnosing or monitoring step and the method further comprises changing the treatment regimen of the subject in response to the prognosing, diagnosing or monitoring step. 
     
     
         15 . The method of  claim 14 , wherein changing the treatment regime comprises administering an immunosuppressive drug to the subject. 
     
     
         16 . The method of  claim 1 , further comprising performing an additional procedure to detect CAN/IFTA or risk thereof if the determining step provides an indication the subject has or is at risk of CAN/IFTA. 
     
     
         17 . The method of  claim 1 , wherein the transplanted kidney is a transplanted kidney organ, transplanted tissues, or transplanted kidney cells. 
     
     
         18 . The method of  claim 1 , wherein the subject is human. 
     
     
         19 . An array, comprising a support or supports bearing a plurality of nucleic acid probes complementary to a plurality of mRNAs fewer than 5000 in number, wherein the plurality of mRNAs includes mRNAs expressed by at least five genes selected from Table A, B, C, D. 
     
     
         20 . A method of subtyping a CAN/IFTA, comprising (a) determining expression levels in a subject of at least 5 genes selected from the genes in Tables A, B, C, D; E, F, G, H, I and/or J; and (b) determining a subtype of CAN/IFTA from the expression levels.