New approach to blood-based TB diagnosis
Optical biosensor device aids in biomarker identification
LOS ALAMOS, N.M., April 7, 2021 — Work at Los Alamos National Laboratory, in conjunction with its research partners, provides valuable new insights into the diagnosis of tuberculosis (TB) using blood tests. A paper in the journal PLOS ONE today demonstrates the role that host-pathogen interactions play in detecting key biomarkers in blood, facilitating the diagnosis of disseminated or sub-clinical TB disease.
“We described two tailored assay strategies for the
direct detection of a particular biomarker by taking advantage
of its association with fat-carrying lipoproteins in our
body,” said Harshini Mukundan, lead scientist on the
project. “Our findings highlight the role that
host-pathogen interactions play during TB disease and the need
to account for these interactions in the design of diagnostic
assays. Our findings also raise the intriguing possibility
that measurement of the biomarker lipoarabinomannan (LAM) in
serum might allow for the diagnosis of disseminated or
subclinical TB, which are especially challenging to identify
today.”
TB is the leading cause of global mortality
associated with a single infectious disease, and is estimated
to afflict 10 million people worldwide, with approximately 1.3
million deaths each year. The World Health Organization has
identified the need for a non-sputum diagnostic test for TB,
particularly for extrapulmonary TB and pulmonary TB associated
with low bacterial presence in airways, as can occur in young
children and in individuals with HIV co-infection, the
researchers note.
For this study, the researchers used existing
stored specimens that previously had been obtained from
participants in Uganda. That diagnostic accuracy study
enrolled HIV-positive adults suspected of having active TB
based on the presence of cough, fever, night sweats, or weight
loss.
The LAM biomarker the team explored is an
amphiphilic lipoglycan component of the Mycobacterium
tuberculosis (MTB) cell wall that has been shown to modulate
innate immunity.
The team used two tailored amphiphile detection assays
– membrane insertion and lipoprotein capture – on
a waveguide-based biosensor platform developed at the Los
Alamos National Laboratory. “We have consistently shown
that the use of the waveguide platform offers at least 10
times greater sensitivity than conventional plate-based ELISA
(enzyme-linked immunosorbent assay),” said
Mukundan, “which provides an advantage when it comes to
sensitive detection of pathogen antigens in complex clinical
samples.”
The paper: “Interaction of amphiphilic lipoarabinomannan with host
carrier lipoproteins in tuberculosis patients:
Implications for blood-based diagnostics,” PLOS ONE, April 2021.
The funding: LANL Laboratory
Directed Research and Development and National Institutes of
Health.
About Los Alamos National Laboratory
Los Alamos National Laboratory, a multidisciplinary research institution engaged in strategic science on behalf of national security, is managed by Triad, a public service oriented, national security science organization equally owned by its three founding members: Battelle Memorial Institute (Battelle), the Texas A&M University System (TAMUS), and the Regents of the University of California (UC) for the Department of Energy’s National Nuclear Security Administration.
Los Alamos enhances national security by ensuring the safety and reliability of the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and solving problems related to energy, environment, infrastructure, health, and global security concerns.
Source:
Los Alamos National Laboratory
