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2015 ; 94
(39
): e1628
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Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A
Prospective Observational Study
#MMPMID26426648
Lee MR
; Tsai CJ
; Wang WJ
; Chuang TY
; Yang CM
; Chang LY
; Lin CK
; Wang JY
; Shu CC
; Lee LN
; Yu CJ
Medicine (Baltimore)
2015[Sep]; 94
(39
): e1628
PMID26426648
show ga
Despite numerous studies, there has been little progress in the use of biomarkers
for predicting treatment response in patients with tuberculosis (TB). Patients
with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively
recruited. Blood samples were taken upon diagnosis and 2 months after the start
of standard anti-TB treatment. A pilot study utilizing measurement of
TB-antigen-stimulated cytokines was conducted to select potential biomarkers for
further testing. Outcome was defined as persistent culture positivity at 2 months
into treatment. Of 167 enrolled patients, 26 had persistent culture positivity.
RANTES, IL-22, MMP-8, IL-18, MIG, and Granzyme A were selected as potential
biomarkers. For predicting persistent culture positivity, receiver-operating
characteristics (ROC) analysis showed that initial RANTES (AUC: 0.725
[0.624-0.827]) and 2-month MMP-8 (AUC: 0.632 [0.512-0.713]) had good
discriminative ability. Using a logistic regression model, low initial RANTES
level (< 440 pg/mL), initial smear positivity, and high 2-month MMP-8 level (>
3000 pg/mL) were associated with persistent culture positivity. Low initial
RANTES level and initial smear positivity had a positive predictive value of 60%
(12/20) for persistent culture positivity, compared with 4% (3/75) among patients
with high RANTES level and smear negativity upon diagnosis. In the 72 patients
with either low RANTES/smear negativity or high RANTES/smear positivity upon
diagnosis, the 2-month MMP-8 level had a positive and negative predictive value
of 24 and 94%, respectively, for 2-month culture status. Aside from an initial
sputum smear status, serum RANTES level at diagnosis and MMP-8 level at 2 months
of treatment may be used to stratify risk for culture persistence.
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