Methods for treating and diagnosing disease

Abstract

The present invention provides methods for the diagnosis and/or treatment of chronic kidney disease, immune complex-mediated GN, rheumatoid arthritis, and pulmonary fibrosis, and methods for identifying compounds for such therapeutic use.

1 . A method for treating pulmonary fibrosis (PF), comprising administering to a subject in need thereof an amount effective of an inhibitor of 77 kD GPBP to treat the PF. 
     
     
         2 . The method of  claim 1 , wherein the PF is non-idiopathic PF. 
     
     
         3 . A method for treating chronic kidney disease (CKD), comprising administering to a subject in need thereof an amount effective of an inhibitor of 77 kD GPBP to treat the CKD. 
     
     
         4 . A method for treating immune complex-mediated GN, comprising administering to a subject in need thereof an amount effective of an inhibitor of 77 kD GPBP to treat the immune complex-mediated GN. 
     
     
         5 . The method of  claim 4 , wherein the immune complex-mediated GN is associated with an autoimmune disorder selected from the group consisting of IgA nephropathy, systemic lupus erythematosus (SLE) and Goodpasture disease. 
     
     
         6 . The method of  claim 1 , wherein the 77 kD GPBP inhibitor is an antibody that binds to 77 kD GPBP. 
     
     
         7 . The method of  claim 3 , wherein the 77 kD GPBP inhibitor is an antibody that binds to 77 kD GPBP. 
     
     
         8 . The method of  claim 4 , wherein the 77 kD GPBP inhibitor is an antibody that binds to 77 kD GPBP. 
     
     
         9 . A method for diagnosing rheumatoid arthritis (RA) or pulmonary fibrosis (PF) comprising
 (a) contacting a plasma sample from a subject at risk of RA or PF with a GPBP-binding molecule that binds to 77 kD GPBP under conditions to promote selective binding of the GPBP-binding molecule to the GPBP;   (b) detecting complex formation between the GPBP-binding molecule and the 77 kD GPBP in the plasma sample;   (c) comparing an amount of complex formed between the GPBP-binding molecule and the GPBP in the plasma sample to control; and   (d) diagnosing the subject as having RA or PF based on the comparison, or providing the comparison to an entity for diagnosis of RA or PF.   
     
     
         10 . The method of  claim 9 , wherein the 77 kD GPBP-binding molecule comprises an antibody that binds to native 77 kD GPBP. 
     
     
         11 . The method of  claim 10 , wherein the antibody is selective for the 77 kD GPBP isoform. 
     
     
         12 . The method of  claim 9  wherein the subject is at risk of RA. 
     
     
         13 . The method of  claim 12 , wherein the subject suffers from one or more symptoms selected from the group consisting of: one or more swollen joints, one or more stiff joints, one or more warm joints, joint stiffness early in the morning that typically lasts for more than an hour, excess synovial fluid, development of fibrous tissue in the synovium, and impaired range of joint movement. 
     
     
         14 . The method of  claim 9  wherein the subject is at risk of PF. 
     
     
         15 . The method of  claim 14 , wherein the subject suffers from one or more symptoms selected from the group consisting of: chronic dry coughing, fatigue, weakness, chest discomfort, loss of appetite, rapid weight loss, and dyspnea with exertion. 
     
     
         16 . The method of  claim 9 , further comprising determining the subject's plasma level of C reactive protein (CRP), comparing the amount of CRP in the subject's plasma to control, and using the CRP comparison in aiding the diagnosis of RA or PF. 
     
     
         17 . A method for diagnosing CKD or immune complex-mediated GN, comprising
 (a) contacting a plasma sample from a subject at risk of CKD or immune complex-mediated GN with a GPBP-binding molecule that binds to 77 kD GPBP under conditions to promote selective binding of the GPBP-binding molecule to the GPBP;   (b) detecting
 (i) complex formation between the GPBP-binding molecule and the 77 kD GPBP in the plasma sample; and 
 (ii) determining the subject's plasma level of C reactive protein (CRP) 
   (c) comparing
 (i) an amount of complex formed between the GPBP-binding molecule and the GPBP in the plasma sample to control; and 
 (ii) an amount of CRP in the subject's plasma to control; and 
   (d) diagnosing the subject as having CKD or immune complex-mediated GN based on the comparisons, or providing the comparisons to an entity for diagnosis of CKD or immune complex-mediated GN.   
     
     
         18 . A method for identifying compounds to treat CKD, immune complex-mediated GN, and/or PF, comprising contacting a 77 kD GPBP-77 kD GPBP substrate binding complex with one or more test compounds under binding conditions, wherein those test compounds that displace 77 kD GPBP from the binding complex are candidate compounds for treating CKD, immune complex-mediated GN, and/or PF. 
     
     
         19 . A method for identifying compounds to treat CKD, immune complex-mediated GN, and/or PF, comprising contacting a 77 kD GPBP-substrate under binding conditions with
 (a) one or more test compounds; and   (b) 77 kD GPBP;   wherein those test compounds that outcompete 77 kD GPBP for binding to the 77 kD GPBP-binding substrate are candidate compounds for treating CKD, immune complex-mediated GN, and/or PF.