Methods of Predicting Acute Rejection Outcomes

Abstract

A method for assessing risk of losing a transplanted organ by a patient having an episode of acute rejection of the transplanted organ is described. The method includes obtaining from the patient a cell sample from the transplanted organ or peripheral blood, determining a level of FOXP3 in the cell sample, and correlating the level with the risk of loss of the transplanted organ, wherein, compared to a control level, a significantly greater level of FOXP3 in the cell sample from the transplanted organ or a significantly lower level of FOXP3 in the cell sample from the peripheral blood correlates with a decreased risk of loss of the transplanted organ.

What is claimed is: 
     
         1 . A method for assessing likelihood of responding to anti-rejection treatment by a patient having an episode of acute rejection of a transplanted organ, the method comprising:
 (a) measuring an amount of gene expression of FOXP3 in a cell sample from the patient's peripheral blood;   (b) comparing the amount of gene expression of FOXP3 from the cell sample with a control amount of gene expression of FOXP3 representative of a person without acute rejection of a transplanted organ, and   (c) identifying the patient as having an increased likelihood of responding to anti-rejection treatment if the amount of gene expression of FOXP3 in the cell sample is at least 10% lower than the control amount.   
     
     
         2 . The method according to  claim 1 , wherein the amount of gene expression of FOXP3 is an amount of FOXP3 mRNA. 
     
     
         3 . The method according to  claim 1 , wherein the amount of gene expression of FOXP3 is an amount of FOXP3 protein. 
     
     
         4 . The method according to  claim 1 , wherein the transplanted organ is selected from the group consisting of kidney, heart, liver, lung, pancreas, pancreatic islet and intestine. 
     
     
         5 . The method according to  claim 1 , further comprising measuring an amount of serum creatinine in peripheral blood, and correlating the amount with the risk of loss of the transplanted organ, wherein the amount of serum creatinine in peripheral blood that is at least 10% greater than the control amount correlates with an increased risk of loss of the transplanted organ. 
     
     
         6 . The method according to  claim 1 , further comprising:
 (a) determining the log-transformed (±SE) ratio of FOXP3 mRNA to 18S rRNA in the cell sample from the patient;   (b) comparing the log-transformed ratio in the cell sample with a control log-transformed (±SE) ratio of FOXP3 mRNA to 18S rRNA representative of a person without acute rejection of a transplanted organ, and   (c) identifying the patient as having a decreased risk of loss of the transplanted organ if the log-transformed ratio in the cell sample that is lower than the control log-transformed ratio.   
     
     
         7 . The method according to  claim 6 , wherein the amount of gene expression of FOXP3 is an amount of FOXP3 mRNA. 
     
     
         8 . The method according to  claim 6 , wherein the amount of gene expression of FOXP3 is an amount of FOXP3 protein. 
     
     
         9 . A method for assessing the risk of losing a transplanted organ by a patient having an episode of acute rejection of the transplanted organ, the method comprising:
 (a) obtaining from the patient a cell sample from the transplanted organ,   (b) measuring amount of gene expression of FOXP3 in the cell sample from the transplanted organ,   (c) comparing the amount of gene expression of FOXP3 from the cell sample with a control amount of gene expression of FOXP3 representative of a person without acute rejection of a transplanted organ, and   (c) identifying the patient as having a decreased risk of loss of the transplanted organ if the amount of gene expression of FOXP3 in the cell sample from the transplanted organ is at least 10% greater than the control amount.   
     
     
         10 . The method according to  claim 9 , wherein the amount of gene expression of FOXP3 is an amount of FOXP3 mRNA. 
     
     
         11 . The method according to  claim 9 , wherein the amount of gene expression of FOXP3 is an amount of FOXP3 protein. 
     
     
         12 . The method according to  claim 9 , wherein the transplanted organ is selected from the group consisting of kidney, heart, liver, lung, pancreas, pancreatic islet and intestine. 
     
     
         13 . A method for decreasing the risk of losing a transplanted organ by a patient having an episode of acute rejection of the transplanted organ, the method comprising:
 (a) measuring an amount of gene expression of FOXP3 in a cell sample from the patient's peripheral blood;   (b) comparing the amount of gene expression of FOXP3 from the cell sample with a control amount of gene expression of FOXP3 representative of a person without acute rejection of a transplanted organ, and   (c) administering a pharmaceutical composition or therapy to decrease the risk of losing the transplanted organ, if the amount of gene expression of FOXP3 in the cell sample is at least 10% greater than the control amount.   
     
     
         14 . The method according to  claim 13 , wherein the amount of gene expression of FOXP3 is an amount of FOXP3 mRNA. 
     
     
         15 . The method according to  claim 13 , wherein the amount of gene expression of FOXP3 is an amount of FOXP3 protein. 
     
     
         16 . The method according to  claim 13 , wherein the pharmaceutical composition is a corticosteroid. 
     
     
         17 . The method according to  claim 13 , wherein the pharmaceutical composition is an antibody. 
     
     
         18 . The method according to  claim 13 , wherein the therapy is plasmapheresis. 
     
     
         19 . The method according to  claim 13 , wherein the transplanted organ is selected from the group consisting of kidney, heart, liver, lung, pancreas, pancreatic islet and intestine.