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.


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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.

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========================================================================== 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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