Methods of diagnosing tissue fibrosis

Abstract

The present invention provides a method of diagnosing the presence or severity of tissue fibrosis in an individual by detecting α2-macroglobulin (α2-MG) in a sample from the individual; detecting hyaluronic acid (HA) in a sample from the individual; detecting tissue inhibitor of metalloproteinases-1 (TIMP-1) in a sample from the individual; and diagnosing the presence or severity of tissue fibrosis in the individual based on the presence or level of α2-MG, HA and TIMP-1.

1 . A method for differentiating no or mild tissue fibrosis from moderate to severe tissue fibrosis in an individual, the method comprising the steps of:
 (a) contacting a sample from said individual with anti-α2-MG antibody under conditions suitable to form a first complex of α2-MG and anti-α2-MG antibody;   (b) determining the amount of α2-MG-containing first complex;   (c) contacting a sample from said individual with a HA-binding protein (HABP) under conditions suitable to form a second complex of HA and HABP;   (d) determining the amount of HA-containing second complex;   (e) contacting a sample from said individual with anti-TIMP-1 antibody under conditions suitable to form a third complex of TIMP-1 and anti-TIMP-1 antibody;   (f) determining the amount of TIMP-1-containing third complex;   (g) determining an index value for the individual based upon an α2-macroglobulin, HA, and TIMP-1 complex amount algorithm; and   (h) differentiating no or mild tissue fibrosis from moderate or severe tissue fibrosis in said individual based on the index value.   
     
     
         2 . The method of  claim 1 , wherein an index cutoff value is used to differentiate no or mild tissue fibrosis from moderate or severe tissue fibrosis. 
     
     
         3 . The method of  claim 1 , further comprising washing said first complex to remove unbound molecules. 
     
     
         4 . The method of  claim 1 , further comprising washing said second complex to remove unbound molecules. 
     
     
         5 . The method of  claim 1 , further comprising washing said third complex to remove unbound molecules. 
     
     
         6 . The method of  claim 1 , wherein the tissue fibrosis is liver fibrosis.