Methods of diagnosis and treatment of tuberculosis and infection

Abstract

Described herein are methods of treating, diagnosing, and/or prognosing a disease in a subject relating to detection of the glycosylation state of the antibodies present in the subject. In some embodiments, the disease can be an infection. In some embodiments, an antibody glycosylation state that is indicative of the presence of a disease, or a need for treatment of a disease can be reduced glycosylation (e.g., galactosylation, sialation, fucosylation, and/or afucosylated branched glycoforms).

1 . A method of treating a disease or condition in a subject, the method comprising:
 assaying a sample obtained from the subject determine the presence or absence of an antibody glycosylation state indicative of the disease or condition; and   administering a treatment for the disease or condition if the antibody glycosylation state is indicative of the presence of the disease or condition.   
     
     
         2 . The method of  claim 1 , wherein the disease is an infection. 
     
     
         3 . The method of  claim 2 , wherein the disease is elderly flu, syphilis, legionella, lyme disease and/or CMV reactivation. 
     
     
         4 . The method of  claim 1 , wherein the antibody glycosylation state indicative of the disease comprises less glycosylation relative to levels found in a normal individual. 
     
     
         5 . The method of  claim 1 , wherein the antibody glycosylation state comprises less galactosylation, sialation, and/or fucosylation relative to levels found in a normal individual. 
     
     
         6 . The method of  claim 1 , wherein the antibody glycosylation state is marked by one or more different glycan structures relative to a normal individual attached to an antibody Fc-domains. 
     
     
         7 . The method of  claim 1 , wherein the antibody glycosylation state is marked by one or more different glycan structures relative to a latent infected patient attached to an antibody Fc-domain. 
     
     
         8 . The method of  claim 1 , wherein the antibody glycosylation state indicative of the disease is a decreased presence of afucosylated branched glycoforms on bulk IgG. 
     
     
         9 . The method of  claim 1 , wherein the antibody glycosylation state indicative of the disease comprises an inflamed antibody Fc-domain. 
     
     
         10 . The method of  claim 1 , wherein the antibody is an IgG antibody. 
     
     
         11 . The method of  claim 10 , wherein the antibody is an IgG antibody from the plasma of the subject. 
     
     
         12 . The method of  claim 1 , wherein the antibody is antigen specific to the disease. 
     
     
         13 . The method of  claim 1 , wherein the treatment comprises a therapeutically effective dosage of antibody with a normal level of glycosylation relative to a healthy individual. 
     
     
         14 . The method of  claim 1 , wherein the disease is tuberculosis (TB). 
     
     
         15 . The method of  claim 14 , wherein the tuberculosis is active TB. 
     
     
         16 . The method of  claim 14 , wherein the glycosylation state indicative of tuberculosis is selected from the group consisting of:
 decreased 2-galactose (G2): decreased fucosylated G2 (G2F); decreased fucosylated G2 with bisecting N-acetylglucosamine (G2FB); and decreased 2-galactose (G2), fucosylated G2 (G2F), and fucosylated G2 with bisecting N-acetylglucosamine (G2FB).   
     
     
         17 . The method of  claim 1 , wherein the condition is transplant rejection and the glycosylation state indicative of transplant rejection is selected from the group consisting of:
 increased G0FB; increased G0F; and increased G0F and G0FB but not increased G0B.   
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the condition is flu non-responsiveness and the glycosylation state indicative of flu non-responsiveness is selected from the group consisting of:
 increased G1; increased G0B; decreased G0F; and increased G1 and G0B but not increased G0F.   
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 19 , wherein the treatment of flu non-responsiveness comprises decreasing the level and/or activity of G1 and/or G0B antibodies in the subject. 
     
     
         22 . A method of diagnosing a disease in a subject, comprising:
 assaying a sample obtained from the subject to determine the presence or absence of an antibody glycosylation state indicative of the disease;   diagnosing the disease in the subject based upon the presence of an antibody glycosylation state indicative of the disease.   
     
     
         23 .- 58 . (canceled) 
     
     
         59 . A method of detecting infection in a subject, comprising:
 isolating pathogen specific IgG antibody from a biological sample and/or tissue obtained from the subject;   profiling variable glycan decoration on the Fc region of the pathogen specific antibody; and   detecting an active infection based on the presence of an altered glycan display on the Fc region of the pathogen specific antibody relative to an individual with latent pathogenic infection.   
     
     
         60 .- 74 . (canceled)