Hepcidins as Biomarkers for Impending Lupus Nephritis Flare

Abstract

Biomarkers for determining a kidney flare episode in systemic lupus erythematosus are described.

What is claimed is: 
     
         1 . A method for assigning a therapy regimen and/or assigning a prognosis to a subject diagnosed with or suspected of suffering from systemic lupus erythematosus, comprising:
 assaying at least one urine sample obtained from the subject to provide one or more detectable signals related to the presence or amount of one or more subject-derived hepcidin-20 and hepcidin-25 biomarkers; and   correlating the one or more signals obtained from the assaying step to ruling in or out a therapy regimen for the subject, and/or assigning a prognosis to the subject.   
     
     
         2 . A method according to  claim 1 , wherein the method rules in or out an assignment of the subject to early goal-directed therapy. 
     
     
         3 . A method according to  claim 1 , wherein the correlating step comprises comparing concentrations of one or more of the subject-derived hepcidin-20 and hepcidin-25 biomarkers to a predetermined threshold level of hepcidin-20 and/of hepcidin-25. 
     
     
         4 . A method according to  claim 1 , wherein the correlating step comprises:
 determining the concentration of the one or more subject-derived hepcidin-20 and hepcidin-25 biomarkers,   calculating a single panel response value based on the concentration of the subject-derived hepcidin-20 and hepcidin-25 biomarkers, and   comparing the panel response value to one or more predetermined threshold levels for the panel response value.   
     
     
         5 . A method according to  claim 1 , wherein the correlating step comprises:
 comparing one or more subject-derived hepcidin-20 and hepcidin-25 biomarker concentrations to a predetermined threshold level for hepcidin-20 and/or hepcidin-25 and determining the concentration of the subject-derived hepcidin-20 and hepcidin-25 biomarkers,   calculating a single panel response value based on the concentration of the subject-derived hepcidin-20 and/or hepcidin-25 biomarkers, and   comparing the panel response value to a predetermined threshold level for the panel response value.   
     
     
         6 . A method according to  claim 1 , wherein the more subject-derived biomarkers comprise hepcidin-25 and hepcidin-20. 
     
     
         7 . A method according to  claim 1 , wherein the sample is from a human. 
     
     
         8 . A method according to  claim 1 , wherein the assay method comprises an immunoassay. 
     
     
         9 . A method according to  claim 1 , wherein the assay method comprises mass spectrometry. 
     
     
         10 . A method according to  claim 1 , wherein the method rules in or out one or more treatments for inclusion in a therapy regimen comprising administration of immunosuppressive therapy. 
     
     
         11 . The method of  claim 1 , wherein the assay method comprises:
 determining a concentration of the hepcidin-20 and/or hepcidin-25 biomarkers in the urine sample from a subject suffering from systemic lupus erythematosus,   wherein an increase in hepcidin-20 and/or hepcidin-25 biomarker concentration in the urine sample relative to a threshold hepcidin concentration indicates a kidney flare episode is likely to occur in the subject, and   wherein lack of an increase in hepcidin-20 and/or hepcidin-25 biomarker concentration in the urine sample relative to a threshold hepcidin-20 and/or hepcidin-25 concentration indicates a kidney flare episode is not likely to occur in the subject.   
     
     
         12 . The method of  claim 11 , wherein the assay method comprises:
 determining a concentration of hepcidin-20 in urine sample from the subject,   wherein an increase in hepcidin-20 concentration in the urine sample relative to a threshold hepcidin-20 concentration indicates a kidney flare episode in the subject is likely to occur within about four months, and   wherein lack of an increase in hepcidin-20 concentration in the urine sample relative to a threshold hepcidin-20 concentration indicates a kidney flare episode is not likely to occur within about four months in the subject.   
     
     
         13 . The method of  claim 12  wherein the increase in hepcidin-20 is present at about four months prior to the presentation of symptoms of the kidney flare episode. 
     
     
         14 . The method of  claim 11 , further comprising:
 determining a concentration of hepcidin-25 in the urine sample from the subject,   wherein a decrease in hepcidin-25 concentration in the urine sample relative to a threshold hepcidin-25 concentration indicates a kidney flare episode in the subject, and   wherein lack of an decrease in hepcidin-25 concentration in the urine sample relative to a threshold hepcidin-25 concentration indicates a kidney flare episode is not present in the subject.   
     
     
         15 . The method of  claim 14 , wherein the decrease in hepcidin-25 is present at about two months prior to the presentation of symptoms of the kidney flare episode. 
     
     
         16 . A method for diagnosing a disease condition characterized by non-physiological levels of hepcidin, comprising:
 obtaining a urine sample from a subject;   contacting the urine sample with an antibody or fragment thereof that specifically binds to one or more binding sites on hepcidin, and   quantifying hepcidin level in the urine sample; wherein the non-physiological level of hepcidin is indicative of the disease condition.   
     
     
         17 . The method of  claim 16 , wherein the antibody specifically binds an epitope contained within amino acids 20 to 25 of hepcidin. 
     
     
         18 . The method of  claim 16 , wherein the quantifying comprises conducting a SELDI-TOF-MS assay 
     
     
         19 . A kit for detecting a disease condition characterized by non-physiological levels of hepcidin, comprising:
 at least one anti-hepcidin antibody or fragment thereof that specifically binds to one or more mid-portion or carboxy terminal epitopes of hepcidin, and   at least one reagent that binds directly or indirectly to the antibody or fragment thereof.   
     
     
         20 . The kit of  claim 20 , wherein the anti-hepcidin antibody or fragment thereof is immobilized on a support. 
     
     
         21 . The kit of  claim 20 , wherein the reagent comprises hepcidin complexed with a first binding molecule. 
     
     
         22 . The kit of  claim 20 , wherein the hepcidin comprises one or more of hepcidin-20 and hepcidin-25. 
     
     
         23 . A test device for performing a method of analyzing a subject sample for one or more subject-derived hepcidin-20 and hepcidin-25 biomarker selected to identify at least a beginning of a kidney flare episode in a patient suffering from systemic lupus erythematosus (SLE), the test device comprising:
 a test surface comprising a plurality of discrete addressable locations corresponding to hepcidin-20 and hepcidin-25 biomarkers,   each the location comprising an antibody immobilized at the location selected to bind for detection one of the hepcidin-20 and hepcidin-25 biomarkers.