New synthetic lipid antigens for rapid serological diagnosis of TB
Abstract
Background
During pulmonary
tuberculosis (PTB) antibodies are generated to trehalose esters
of mycolic acids which are cell wall lipids of Mycobacterium
tuberculosis (Mtb). Attempts have been made to use these complex
natural mixtures in serological tests for PTB diagnosis.
Aim
The aim of this work was to
determine whether a serological test based on a panel of defined
individual trehalose esters of characteristic synthetic mycolic
acids has improved diagnostic accuracy in distinguishing
patients with culture positive PTB from individuals who were Mtb
culture negative.
Method
One hundred serum samples
from well-characterized patients with presumptive tuberculosis,
and diagnosed as having pulmonary smear and culture positive TB,
or being culture and smear negative were evaluated by ELISA
using different combinations of synthetic antigens and secondary
antibodies. Using cut-off values determined from these samples,
we validated this study blind in samples from a further 249
presumptive TB patients.
Results
With the first 100 samples,
detailed responses depended both on the precise structure of the
antigen and on the secondary antibody. Using a single antigen, a
sensitivity/specificity combination for smear and culture
positive PTB detection of 85 and 88% respectively was achieved;
this increased to 96% and 95% respectively by a statistical
combination of the results with seven antigens. In the blind
study a sensitivity/specificity of 87% and 83% was reached with
a single antigen. With some synthetic antigens, the responses
from all 349 samples were significantly better than those with
the natural mixture. Combining the results for seven antigens
allowed a distinction between culture positive and negative with
a ROC AUC of 0.95.
Conclusion
We have identified
promising antigen candidates for serological assays that could
be used to diagnose PTB and which could be the basis of a
much-needed, simple, rapid diagnostic test that would bring care
closer to communities.
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Source:
PLOS ONE
