Methods of Using FOXP3 Levels to Predict the Outcome of Organs Undergoing Acute Rejection

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.

1 . A method for assessing 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 or from peripheral blood;   (b) determining a level of FOXP3 in the cell sample; and   (c) 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, or 
       a level of FOXP3 that is not significantly greater in the cell sample from the transplanted organ or a level of FOXP3 that is not significantly lower in the cell sample from peripheral blood correlates with an increased risk of loss of the transplanted organ. 
     
     
         2 . A method according to  claim 1 , wherein the level of FOXP3 is determined by measuring the level of FOXP3 in RNA. 
     
     
         3 . A method according to  claim 1 , wherein the level of FOXP3 is determined by measuring the level of FOXP3 protein. 
     
     
         4 . A method according to  claim 1 , wherein the method further comprises assessing the likelihood of the patient's responding to anti-rejection treatment, 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 an increased likelihood of responding to anti-rejection treatment, and a level of FOXP3 that is not significantly greater in the cell sample from the transplanted organ or a level of FOXP3 that is not significantly lower in the cell sample from peripheral blood correlates with a decreased likelihood of responding to anti-rejection treatment. 
     
     
         5 . A method according to  claim 5 , wherein the transplanted organ is a kidney. 
     
     
         6 . A method according to  claim 3 , wherein the cell sample from the kidney is urine. 
     
     
         7 . A method according to  claim 1 , wherein the transplanted organ is a heart. 
     
     
         8 . A method according to  claim 1 , wherein the transplanted organ is a liver. 
     
     
         9 . A method according to  claim 1 , wherein the transplanted organ is a lung. 
     
     
         10 . A method according to  claim 1 , wherein the transplanted organ is a pancreas. 
     
     
         11 . A method according to  claim 1 , wherein the transplanted organ is a pancreatic islets. 
     
     
         12 . A method according to  claim 1 , wherein the transplanted organ is intestine. 
     
     
         13 . A method according to  claim 1 , further comprising informing the patient whether the patient is at decreased or increased risk of loss of the transplanted organ. 
     
     
         14 . A method according to  claim 1 , further comprising prescribing to the patient at increased risk of loss of the transplanted organ a treatment to prevent loss of the transplanted organ. 
     
     
         15 . A method according to  claim 14 , wherein the treatment comprises an effective amount of a pharmaceutical composition to prevent loss of the transplanted organ. 
     
     
         16 . A method according to  claim 12 , wherein the pharmaceutical composition comprises a steroid pulse. 
     
     
         17 . A method according to  claim 13 , wherein the steroid is a corticosteroid. 
     
     
         18 . A method according to  claim 12 , wherein the pharmaceutical composition comprises an antibody. 
     
     
         19 . A method according to  claim 14 , wherein the antibody is thymoglobin or OKT3. 
     
     
         20 . A method according to  claim 14 , wherein the treatment comprises plasmapheresis. 
     
     
         21 . A method according to  claim 5 , further comprising determining the patient's serum creatinine level in peripheral blood, and correlating the level with the risk of loss of the transplanted kidney, wherein, compared to a control level, a significantly greater level of serum creatinine in peripheral blood correlates with an increased risk of loss of the transplanted kidney, or a level of serum creatinine in peripheral blood that is not significantly greater correlates with a decreased risk of loss of the transplanted kidney. 
     
     
         22 . A method for assessing likelihood of responding to anti-rejection treatment 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 or from peripheral blood;   (b) determining a level of FOXP3 in the cell sample; and   (c) correlating the level with the likelihood of responding to anti-rejection treatment;   
       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 an increased likelihood of responding to anti-rejection treatment, or 
       a level of FOXP3 that is not significantly greater in the cell sample from the transplanted organ or a level of FOXP3 that is not significantly lower in the cell sample from peripheral blood correlates with a decreased likelihood of responding to anti-rejection treatment. 
     
     
         23 . A method for assessing the likelihood of reversing an acute rejection of 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 or from peripheral blood;   (b) determining a level of FOXP3 in the cell sample;   (c) correlating the level with the likelihood of reversing acute rejection 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 an increased likelihood of reversing acute rejection of the transplanted organ, or 
       a level of FOXP3 that is not significantly greater in the cell sample from the transplanted organ or a level of FOXP3 that is not significantly lower in the cell sample from peripheral blood correlates with a decreased likelihood of reversing acute rejection of the transplanted organ.