Method for diagnosis of chronic allograft rejection

Abstract

The present invention provides a method for the diagnosis of chronic rejection in allografts. The method comprises identification of tertiary lymphoid organs (TLO) in the transplanted organs as a marker of chronic rejection by immunohistochemical detection for the presence of specific TLO antigens in biopsy samples or by radiographic imaging of radiolabeled antibodies to specific TLO antigens. In one embodiment, the presence of TLO is detected by the intravenous administration of a radiolabeled antibody to PNAd followed by radiographic imaging to determine the presence or absence of PNAd in the transplanted organ. The presence of PNAd in the transplanted organ is taken as an indication of chronic rejection.

1 . A method for diagnosing chronic rejection of a transplanted organ in an individual comprising the steps of:
 a) administering a radiolabeled antibody to peripheral node addressin (PNAd) into the vasculature of a transplanted organ;   b) allowing sufficient time for the antibody to distribute in the transplanted organ; and   c) obtaining a radiographic image distribution of the detectably labeled antibody in the transplanted organ to determine the presence or absence of PNAd in the organ,   
     wherein the presence of PNAd in the transplanted organ is indicative of chronic allograft rejection. 
   
   
       2 . The method of  claim 1 , wherein the detectable label on the antibody is selected from the group consisting of gold, iridium, technetium, barium, thallium, iodine, and isotopes thereof. 
   
   
       3 . The method of  claim 1 , wherein the antibody to PNAd is selected from the group consisting of MECA-79 antibody, an antigen binding fragment thereof, an antibody that binds to the same epitope as MECA-79 antibody and an antigen binding fragment thereof. 
   
   
       4 . The method of  claim 1 , wherein the antibody to PNAd is selected from the group consisting of anti-GlcNAc6ST-2, an antigen binding fragment thereof, an antibody that binds to the same epitope as anti-GlcNAc6ST-2 and an antigen binding fragment thereof. 
   
   
       5 . The method of  claim 1 , wherein the transplanted organ is a solid organ. 
   
   
       6 . The method of  claim 1 , wherein the solid organ is selected from the group consisting of heart, liver, lung, kidney, pancreas and skin. 
   
   
       7 . A method for diagnosing chronic rejection of a transplanted organ in an individual comprising the steps of:
 a) obtaining a tissue sample from the transplanted organ; and   b) immunohistochemically detecting the presence of PNAd in the transplanted organ wherein the presence of PNAd in the transplanted organ is indicative of chronic rejection.   
   
   
       8 . The method of  claim 7 , wherein the immunohistochemical detection of PNAd is carried out by using MECA-79 antibody, an antigen binding fragment thereof, antibody that binds to the same epitope as MECA-79 or an antigen binding fragment thereof. 
   
   
       9 . The method of  claim 7 , wherein the immunohistochemical detection of PNAd is carried out by using anti-GlcNAc6ST-2, an antigen binding fragment thereof, an antibody that binds to the same epitope as anti-GlcNAc6ST-2 or an antigen binding fragment thereof. 
   
   
       10 . The method of  claim 7 , wherein the transplanted organ is a solid organ. 
   
   
       11 . The method of  claim 7 , wherein the solid organ is selected from the group consisting of heart, liver, lung, kidney, pancreas and skin.