Diagnostics for membranous nephropathy

Abstract

The invention provides immunoassays for detecting serum auto-antibodies reactive against a phospholipase A2 receptor (PLA2R) and uses thereof for diagnosis and prognosis evaluation of idiopathic membranous nephropathy (MN).

1 . (canceled) 
     
     
         2 . (canceled) 
     
     
         3 . An assay comprising measuring for antibodies that are reactive to a phospholipase A2 receptor (PLA2R) in a blood sample obtained from a patient who presents at least one symptom of idiopathic membranous nephropathy (MN) and determining if there is a detectable presence of antibodies reactive against PLA2R wherein the presence of the detectable level of antibodies indicates that the patient likely has idiopathic MN. 
     
     
         4 . An assay comprising measuring for antibodies that are reactive to a phospholipase A2 receptor (PLA2R) in a blood sample obtained from a patient who previously has been successfully treated for idiopathic membranous nephropathy (MN) for determining the likelihood of relapse of idiopathic MN in the patient, and determining if there is a detectable presence of antibodies reactive against PLA2R wherein a detectable presence of antibodies reactive against PLA2R indicates that the patient likely has a relapse of idiopathic MN. 
     
     
         5 . An assay comprising:
 a. measuring a level of antibodies that are reactive to a phospholipase A2 receptor (PLA2R) in a blood sample obtained from a patient who presents at least one symptom of idiopathic membranous nephropathy (MN), and   b. comparing the measured level of the antibodies with a control data from a population of non-MN healthy individuals, wherein an increase in the antibodies that are reactive to PLA2R in the blood sample over that of the control data indicates the likelihood of idiopathic MN.   
     
     
         6 . An assay comprising:
 a. measuring a level of antibodies that are reactive to a phospholipase A2 receptor (PLA2R) in a blood sample obtained from a patient who previously has been successfully treated for idiopathic membranous nephropathy (MN), and   b. comparing the measured level of the antibodies with a control data from a population of non-MN healthy individuals, wherein an increase in the antibodies that are reactive to PLA2R in the blood sample over that of the control data indicates the likelihood of relapse of idiopathic MN.   
     
     
         7 . The assay of  claim 3 , wherein the PLA2R antibodies are by measured by light scattering assay or an immunoassay. 
     
     
         8 . The assay of  claim 7 , wherein the detectable presence of the PLA2R antibodies is determined by the detection limit of the light scattering assay or the immunoassay. 
     
     
         9 . The assay of  claim 7 , wherein the level of PLA2R antibodies is measured by the steps comprising:
 a. contacting the blood sample from the patient with a PLA2R or PLA2R fragment thereof;   b. forming an antibody-protein complex between the antibody present in the sample with the PLA2R or PLA2R fragment thereof;   c. washing to remove any unbound antibody;   d. adding a detection antibody that is labeled and is reactive to the antibody from the sample;   e. washing to remove any unbound labeled detection antibody; and   f. converting the label to a detectable signal, wherein the presence of a detectable signal indicates the likelihood of idiopathic MN in the patient.   
     
     
         10 . The assay of  claim 9 , wherein the PLA2R or PLA2R protein fragment thereof is deposited or immobilized on a solid support. 
     
     
         11 . The assay of  claim 10 , wherein the support is in the format of a dipstick, a test strip, a latex bead, a microsphere or a multi-well plate. 
     
     
         12 . The assay of  claim 11 , wherein the detection antibody is labeled by covalently linking to an enzyme, label with a fluorescent compound or metal, or label with a chemiluminescent compound. 
     
     
         13 . The assay of  claim 3 , wherein the symptom is nephrotic syndrome or proteinuria. 
     
     
         14 . The assay of  claim 5 , wherein the symptom is nephrotic syndrome or proteinuria. 
     
     
         15 . The assay of  claim 4 , wherein the patient presents a symptom of idiopathic MN. 
     
     
         16 . The assay of  claim 6 , wherein the patient presents a symptom of idiopathic MN. 
     
     
         17 . The assay of  claim 15 , wherein the symptom is nephrotic syndrome or proteinuria. 
     
     
         18 . The assay of  claim 16 , wherein the symptom is nephrotic syndrome or proteinuria. 
     
     
         19 . The assay of  claim 3 , further comprising selecting the patient for treatment for idiopathic MN without subjecting the patient to a kidney biopsy if there is a detectable presence of the PLA2R antibodies in the blood sample. 
     
     
         20 . The assay of  claim 4 , further comprising selecting the patient for treatment for idiopathic MN without subjecting the patient to a kidney biopsy if there is a detectable presence of the PLA2R antibodies in the blood sample. 
     
     
         21 . The assay of  claim 5 , further comprising selecting the patient for treatment for idiopathic MN without subjecting the patient to a kidney biopsy if there is an increase in PLA2R antibodies in the blood sample over that of the control data. 
     
     
         22 . The assay of  claim 6 , further comprising selecting the patient for treatment for idiopathic MN without subjecting the patient to a kidney biopsy if there is an increase in PLA2R antibodies in the blood sample over that of the control data.