MSGID: 1:317/3 640ff876   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Researchers develop new technology to easily detect active TB    
      
     Date:   
         March 13, 2023   
     Source:   
         Wayne State University - Office of the Vice President for Research   
     Summary:   
         A team of faculty has discovered new technology that will quickly   
         and easily detect active Mycobacterium tuberculosis (TB) infection   
         antibodies.   
      
      
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   FULL STORY   
   ==========================================================================   
   A team of faculty from Wayne State University has discovered new   
   technology that will quickly and easily detect active Mycobacterium   
   tuberculosis (TB) infection antibodies. Their work, "Discovery   
   of Novel Transketolase Epitopes and the Development of IgG-Based   
   Tuberculosis Serodiagnostics," was published in a recent edition of   
   Microbiology Spectrum, a journal published by the American Society for   
   Microbiology. The team is led by Lobelia Samavati, M.D., professor   
   in the Center for Molecular Medicine and Genetics in the School of   
   Medicine. Samavati was joined by Jaya Talreja, Ph.D, and Changya Peng,   
   research scientists in Wayne State's Department of Internal Medicine.   
      
      
   ==========================================================================   
   TB remains a global health threat, with 10 million new cases and 1.7   
   million deaths annually. According to the latest World Health Organization   
   report, TB is the 13th leading cause of death and the second leading   
   infectious killer after COVID-19. Latent tuberculous infection (LTBI)   
   is considered a reservoir for TB bacteria and subjects can progress to   
   active TB. One-third of the world's population is infected with TB and,   
   on average, 5 to 10% of those infected with LTBI will develop active TB   
   disease over the course of their lives, usually within the first five   
   years after initial infection.   
      
   The gold standard tests to determine whether an infection is active   
   TB are the sputum smear and culture tests. However, these methods   
   require collecting sputum, which is time consuming, expensive, requires   
   trained personnel and lacks sensitivity. The current conventional tests   
   differentiating LTBI from uninfected controls -- such as tuberculin   
   skin tests (TST) and/or interferongamma release assay (IGRA) -- do not   
   differentiate between active TB infection and latent TB. Despite advances   
   in rapid molecular techniques for TB diagnostics, there is an unmet need   
   for a simple inexpensive point-of-care (POC), rapid non-sputum-based test.   
      
   Samavati's research group has worked for more than 15 years to   
   develop technology for detection of antibodies in various respiratory   
   diseases. Her lab has developed a novel non-sputum based technology and   
   has discovered several novel immune-epitopes that differentialy bind   
   to specific immunoglobulin (IgG) in TB-infected subjects. The levels   
   of epitope-specific IgG in seum can differentiate active TB from LTBI   
   subjects, healthy contols and other respiratory diseases. This technology   
   can be used as a simple serum assay non- sputum based serological POC-   
   TB test, which is highly specific and sensitveto diffentiate active TB   
   from LTBI.   
      
   "Previously, we developed a T7 phage antigen display platform and after   
   immunoscreening of large sets of serum samples, identified 10 clones   
   that differentially bind to serum antibody (IgG) of active TB patients   
   differentiating TB from other respiratory diseases," said Samavati. "One   
   of these high-performance clones had homology to the Transketolase (TKT)   
   enzyme of TB bacteria that is an essential enzyme required for the   
   intracellular growth of the bacteria in a host. We hypothesized that   
   abundance of IgG in sera against the identified novel neoantigen that   
   we named as TKTmy may differentiate between active TB, LTBI and other   
   non-TB granulomatous lung diseases such as sarcoidosis. We developed   
   a novel direct Peptide ELISA test to quantify the levels of IgG in   
   serum samples against TKTmy. We designed two additional overlapping   
   M.tb TKT-peptide homologs with potential antigenicity corresponding   
   to M.tb-specifictransketolase (M.tb-TKT1 and M.tb-TKT3) and hence   
   standardized three Peptide ELISA (TKTm, M.tb TKT1 and M.tb TKT3) for   
   the TB serodiagnosis."  After development and standardization of a   
   direct peptide ELISA for three peptides, the research team tested 292   
   subjects, and their TKT-peptide ELISA results show that TB patients   
   have significantly higher levels of TKT-specific antibodies compared to   
   patients who were healthy controls and with LTBI. The increased levels   
   of TKT-specific antibodies is presumably associated with growing M.tb   
   bacteria in active TB patients. TKT plays a key role in the switch from   
   the dormancy to proliferative phase and TKT specific IgG may uncover the   
   differences between active TB and LTBI. Thus, IgG-based serodiagnosis   
   of TB with TKT-peptide ELISA is promising.   
      
   Currently, commercially available serological TB tests show poor   
   sensitivity and specificity. The ELISA results obtained with the   
   Wayne State team's discovered TKT peptides yielded high specificity and   
   sensitivity. Their results show that IgG antibodies against transketolase   
   can discriminate active tuberculosis.  "Our TKT peptide ELISA test   
   requires chemically synthesized TKT peptides to coat the wells in the   
   ELISA plate, less than 100myl blood serum sample from patient, detection   
   reagents and an ELISA plate reader," said Samavati. "We are extremely   
   enthusiastic about our technology and the fact that with a simple test   
   we can differentiate active TB from LTBI and other respiratory diseases.   
      
   We believe that our method and TKT peptide ELISA can fit the requirements   
   of the World Health Organization and the Centers for Disease Control and   
   Prevention as a POC screening method."  The research team has applied a   
   patent application on its technology and is actively seeking companies   
   interested in investing.   
      
   This research was supported by the National Heart, Lung and Blood   
   Institute of the National Institutes of Health, grant numbers 113508   
   and 148089. The Foundation for Innovative New Diagnostics (FIND, Geneva,   
   Switzerland) provided TB and LTBI samples.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Tuberculosis # Infectious_Diseases #   
                   Diseases_and_Conditions # COPD   
             o Plants_&_Animals   
                   # Microbiology # Bacteria # New_Species #   
                   Veterinary_Medicine   
       * RELATED_TERMS   
             o Tuberculosis o HIV_test o Drug_discovery o   
             Monoclonal_antibody_therapy o Pharmaceutical_company o HPV o   
             Gastroenteritis o Urinary_tract_infection   
      
   ==========================================================================   
   Story Source: Materials provided   
   by Wayne_State_University_-_Office_of_the_Vice_President_for   
   Research. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Jaya Talreja, Changya Peng, Tuan-Minh Nguyen, Sorin Draghici,   
      Lobelia   
         Samavati. Discovery of Novel Transketolase Epitopes and the   
         Development of IgG-Based Tuberculosis Serodiagnostics. Microbiology   
         Spectrum, 2023; 11 (1) DOI: 10.1128/spectrum.03377-22   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/03/230313162715.htm   
      
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