Detection and quantitation of urine gelsolin

Abstract

The invention relates generally to gelsolin binding agents (e.g., antibodies) which can bind to gelsolin polypeptides. Gelsolin binding agents of the invention are useful, alone or in combination, to detect a gelsolin polypeptide in a test sample. In particular, the gelsolin binding agents are useful in assays of urine samples to diagnose a gelsolin-related medical condition. Kits to detect gelsolin in biological samples are also provided by the present disclosure.

1 . A method for determining the presence of, or predisposition to, a disease or condition associated with altered levels of gelsolin in a mammalian subject, the method comprising the steps of:
 (a) contacting a urine sample from the mammalian subject under immunologically-reactive conditions with one or more antibodies or antibody-related polypeptides having the same antigen-binding specificity as antibodies produced by a deposited cell line selected from the group consisting of: CGMCC Accession Nos: 2114, 2116, 2247 and 2248; and   (b) detecting the binding of the one or more antibodies or antibody-related polypeptides to the gelsolin-like polypeptide to determine the level of gelsolin-like polypeptide in the sample, wherein a difference between the level of gelsolin-like polypeptide in the sample and a reference level indicates a presence of, or predisposition to, a disease or condition associated with altered levels of gelsolin in the mammalian subject.   
     
     
         2 . The method of  claim 1 , wherein the sample is contacted with the antibodies or antibody-related polypeptides in an ELISA. 
     
     
         3 . The method of  claim 2 , wherein the step of contacting comprises binding a first antibody to a substrate and contacting the sample and a second antibody to the substrate, wherein the second antibody comprises a detectable label. 
     
     
         4 . The method of  claim 3 , wherein the first antibody binds to the same antigenic determinant as an antibody produced by a hybridoma cell line CGMCC Accession No: 2247 and the second antibody binds to the same antigenic determinant as an antibody produced by a hybridoma cell line selected from the group consisting of CGMCC Accession No. 2116. 
     
     
         5 . The method of  claim 1 , wherein the disease or condition associated with altered levels of gelsolin is selected from the group consisting of: kidney failure, septic shock, multiple organ dysfunction syndrome, rheumatoid arthritis, stroke, heart infarction, cancer, systemic autoimmune disease, chronic hepatitis, side-effects of chemotherapy, and side-effects of radiation therapy. 
     
     
         6 . The method of  claim 1 , wherein the gelsolin-like polypeptide is a C-terminal fragment of gelsolin. 
     
     
         7 . The method of  claim 2 , wherein an increase in the level of gelsolin-like polypeptide in the sample compared to the reference level indicates a presence of, or predisposition to, a disease or condition associated with altered levels of gelsolin in a mammalian subject. 
     
     
         8 . The method of  claim 1 , wherein the reference level is the amount of the gelsolin-like polypeptide in a control population of subjects that do not have a disease or condition associated with altered levels of gelsolin. 
     
     
         9 . The method of  claim 1 , wherein the reference level is the amount of the gelsolin-like polypeptide in a subject that does not have a disease or condition associated with altered levels of gelsolin. 
     
     
         10 . The method of  claim 1 , wherein the reference level is the amount of the gelsolin-like polypeptide in the subject at an earlier time. 
     
     
         11 . The method of  claim 1  further comprising quantifying the amount of the gelsolin-like polypeptide in the sample from the subject. 
     
     
         12 . The method of  claim 11  further comprising correlating the amount of gelsolin-like polypeptide in the sample from the mammalian subject to a likelihood of survival of the subject. 
     
     
         13 . The method of  claim 3  further comprising the step of:
 comparing the level of gelsolin-like polypeptide in the mammalian subject to a reference level, wherein the reference level comprises a control subject not having kidney failure, and wherein an increase in the level of gelsolin-like polypeptide in the subject compared to the reference level indicates that the mammalian subject has kidney failure. 
 
     
     
         14 . The method of  claim 3  further comprising the steps of:
 assigning the subject to a subject class based on the level of gelsolin polypeptide of the subject; and 
 selecting a prophylactic or therapeutic treatment based on the subject class. 
 
     
     
         15 . An antibody or antigen-binding fragment thereof having the same antigen-binding specificity of antibodies produced by a deposited cell line selected from the group consisting of: CGMCC Accession Nos: 2247 and 2248. 
     
     
         16 . The antibody or an antigen-binding fragment of  claim 15  comprising at least heavy chain CDR3 amino acid sequence selected from the group consisting of: GASEAEKTGA (SEQ ID NO.: 5), or a variant thereof having one or more conservative amino acid substitutions. 
     
     
         17 - 24 . (canceled)