Biomarkers associated with nephropathy

Abstract

Use of urine biomarkers for diagnosing nephropathy, monitoring nephropathy progress, and assessing efficacy of a nephropathy treatment. These urine biomarkers include leukocyte-associated Ig-like receptor-2, alpha-1 acid glycoprotein, their fragments, and combinations thereof.

1 . A method of diagnosing nephropathy in a subject, comprising:
 obtaining a urine sample from a subject suspected of having nephropathy,   determining in the urine sample a level of a biomarker selected from the group consisting of (i) a first protein molecule that is leukocyte-associated Ig-like receptor-2 or a fragment thereof having at least ten amino acid residues, (ii) a second protein molecule that is a fragment of alpha-1 acid glycoprotein having at least ten amino acid residues, (iii) a combination of the first and second protein molecules, and (iv) a combination of the first protein molecule and alpha-1 acid glycoprotein; and   assessing whether the subject has nephropathy based on the level of the biomarker,   
       wherein an increase in the level of the biomarker, as compared to that in a nephropathy-free subject, indicates that the subject has nephropathy. 
     
     
         2 . The method of  claim 1 , wherein the fragment of leukocyte-associated Ig-like receptor-2 is DFLELLVKGTVPGTEASGFDAP (SEQ ID NO:1) and the fragment of alpha-1 acid glycoprotein is 
       
         
           
                 
                 
               
                   GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS. 
                   (SEQ ID NO: 2) 
                 
             
                
               
            
           
         
       
     
     
         3 . The method of  claim 1 , wherein the level of the biomarker is determined by a mass spectrometry assay or an immune assay. 
     
     
         4 . The method of  claim 3 , wherein the mass spectrometry assay is selected from the group consisting of MALDI-MS, LC-MS, and LC-MS/MS. 
     
     
         5 . The method of  claim 3 , wherein the immune assay is selected from the group consisting of ELISA, Westernblot, RIA, FIA and LIA. 
     
     
         6 . The method of  claim 1 , wherein the subject is a human. 
     
     
         7 . The method of  claim 1 , wherein the subject is a laboratory animal. 
     
     
         8 . The method of  claim 1 , wherein the biomarker is the first protein molecule. 
     
     
         9 . The method of  claim 8 , wherein the first protein molecule is leukocyte-associated Ig-like receptor-2. 
     
     
         10 . The method of  claim 8 , wherein the first protein molecule is 
       
         
           
                 
                 
                 
               
                     
                   DFLELLVKGTVPGTEASGFDAP. 
                   (SEQ ID NO: 1) 
                 
             
                
               
            
           
         
       
     
     
         11 . The method of  claim 10 , wherein the subject is free of proteinuria. 
     
     
         12 . The method of  claim 1 , wherein the biomarker is the second protein molecule. 
     
     
         13 . The method of  claim 12 , wherein the second protein molecule is 
       
         
           
                 
                 
               
                   GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS. 
                   (SEQ ID NO: 2) 
                 
             
                
               
            
           
         
       
     
     
         14 . The method of  claim 13 , wherein the subject is free of proteinuria. 
     
     
         15 . The method of  claim 1 , wherein the biomarker is the combination of the first and second protein molecules or the combination of the first protein molecule and alpha-1 acid glycoprotein. 
     
     
         16 . The method of  claim 15 , wherein the first protein molecule is leukocyte-associated Ig-like receptor-2 or a fragment thereof that is DFLELLVKGTVPGTEASGFDAP (SEQ ID NO:1) and the second protein molecule is GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS (SEQ ID NO:2). 
     
     
         17 . A method for monitoring nephropathy progress in a subject, comprising
 obtaining a first urine sample from a subject suffering from nephropathy;   determining in the first urine sample a level of a biomarker selected from the group consisting of (i) a first protein molecule that is leukocyte-associated Ig-like receptor-2 or a fragment thereof having at least ten amino acid residues, (ii) a second protein molecule that is a fragment of alpha-1 acid glycoprotein having at least ten amino acid residues, (iii) a combination of the first and second protein molecules, and (iv) a combination of the first protein molecule and alpha-1 acid glycoprotein;   obtaining a second urine sample from the subject 2 weeks to 12 months after the first urine sample is obtained;   determining in the second urine sample a level of the biomarker; and   assessing nephropathy progress in the subject,   wherein an increase in the level of the biomarker in the second urine sample, as compared to that in the first urine sample, indicates that nephropathy is exacerbated in the subject.   
     
     
         18 . The method of  claim 17 , wherein the fragment of leukocyte-associated Ig-like receptor-2 is DFLELLVKGTVPGTEASGFDAP (SEQ ID NO:1) and the fragment of alpha-1 acid glycoprotein is 
       
         
           
                 
                 
               
                   GQEHFAHLLILRDTKTYMLAFDVNDEKNWGLS. 
                   (SEQ ID NO: 2) 
                 
             
                
               
            
           
         
       
     
     
         19 . The method of  claim 18 , wherein the subject is a human in early stage nephropathy and the second urine sample is obtained 6 to 12 months after the first urine sample is obtained. 
     
     
         20 . The method of  claim 18 , wherein the subject is a human in later stage nephropathy and the second urine sample is obtained 3 to 6 months after the first urine sample is obtained. 
     
     
         21 . The method of  claim 18 , wherein the subject is a laboratory animal and the second urine sample is obtained 2 to 24 weeks after the first urine sample is obtained. 
     
     
         22 - 30 . (canceled)