A combination of baseline plasma immune markers can predict therapeutic response in multidrug resistant tuberculosis

Abstract

ObjectiveTo identify plasma markers predictive of therapeutic response in patients with multidrug resistant tuberculosis (MDR-TB).MethodsFifty 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.ResultsUnsupervised 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.ConclusionPlasma 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.

Changes in inflammatory protein and lipid mediator profiles persist after antitubercular treatment of pulmonary and extrapulmonary tuberculosis: A prospective cohort study

“…A number of prospective studies have previously reported changes in biomarker levels during antitubercular treatment in either pulmonary or extrapulmonary TB cases [15,30,33,35,37,[39][40][41][49][50][51]. Our study adds to the current knowledge in the field by directly comparing these changes between PTB and EPTB disease forms while focusing on both lipid mediators and inflammatory cytokines.…”

Frequency of Circulating CD4+Ki67+HLA-DR− T Regulatory Cells Prior to Treatment for Multidrug Resistant Tuberculosis Can Differentiate the Severity of Disease and Predict Time to Culture Conversion

“…A total of 51 HIV negative patients (Table 1 ) initiating treatment for MDR-TB at Sizwe Hospital in Johannesburg, South Africa were enrolled in the study, which has previously been described ( 18 ). Diagnosis of MDR-TB was based on SC (Bactec MGIT 960, Beckton Dickinson, Baltimore, MD) and phenotypic drug susceptibility testing (DST; Bactec MGIT 960) and/or genotypic resistance by PCR (Line Probe Assay, Hain Lifesciences).…”

“…Diagnosis of MDR-TB was based on SC (Bactec MGIT 960, Beckton Dickinson, Baltimore, MD) and phenotypic drug susceptibility testing (DST; Bactec MGIT 960) and/or genotypic resistance by PCR (Line Probe Assay, Hain Lifesciences). Baseline (enrollment) clinical and microbiological characteristics are summarized for many of the enrolled patients ( 18 ). Nine study participants were SC negative at the time of enrollment; all of these patients were SC positive at a median of 55 days (IQR: 16.5–87.5) prior to baseline, suggesting that the infecting TB was partially responsive to first-line drugs.…”

“…It is possible that the prolonged exposure of mycobacterial antigens in patients with MDR-TB may result in the continued proliferation of Treg cells. We previously described several inflammatory plasma markers in MDR-TB patients ( 18 ) that could predict microbiological outcome and showed that chronic inflammation at baseline existed in MDR-TB patients who responded slowly to second-line antibiotics. In the present study, we focused on Treg cells and hypothesized that the chronic inflammation observed in our MDR-TB patients ( 18 ), along with lung cavitation, was associated with elevated proportions of these cells and are useful biomarkers of disease severity and treatment response rates.…”

Can we predict tuberculosis cure? What tools are available?

“…Although promising, further research is needed to establish the efficacy of this new assay as marker for treatment monitoring and/or outcome. 166,195,196] [158] [172,173,197] [ 162,175] Markers of lung tissue repair (platelet activity VEGF, TGF-β, MMPs) [195,196] [135].…”