A combination of baseline plasma immune markers can predict therapeutic response in multidrug-resistant TB
Abstract
Objective
To identify plasma markers
predictive of therapeutic response in patients with
multidrug-resistant tuberculosis (MDR-TB).
Methods
Fifty HIV-negative patients
with active pulmonary MDR-TB were analysed for six soluble
analytes in plasma at the time of initiating treatment
(baseline) and over six months thereafter. Patients were
identified as sputum culture positive or negative at baseline.
Culture positive patients were further stratified by the median
time to sputum culture conversion (SCC) as fast responders (<
76 days) or slow responders (≥ 76 days). Chest X-ray scores,
body mass index, and sputum smear microscopy results were
obtained at baseline.
Results
Unsupervised hierarchical
clustering revealed that baseline plasma levels of IP-10/CXCL10,
VEGF-A, SAA and CRP could distinguish sputum culture and
cavitation status of patients. Among patients who were culture
positive at baseline, there were significant positive
correlations between plasma levels of CRP, SAA, VEGF-A,
sIL-2Rα/CD40, and IP-10 and delayed SCC. Using linear
discriminant analysis (LDA) and Receiver Operating Curves (ROC),
we showed that a combination of MCP-1/CCL2, IP-10,
sIL-2Rα, SAA, CRP and AFB smear could distinguish fast
from slow responders and were predictive of delayed SCC with
high sensitivity and specificity.
Conclusion
Plasma levels of specific
chemokines and inflammatory markers measured before MDR-TB
treatment are candidate predictive markers of delayed SCC. These
findings require validation in a larger study.
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Source:
PLOS ONE
