Dataset Information

Significance of the Differential Peptidome in Multidrug-Resistant Tuberculosis.

ABSTRACT: Most multidrug-resistant tuberculosis (MDR-TB) patients fail to receive a timely diagnosis and treatment. Therefore, we explored the differentially expressed peptides in MDR-TB compared with drug-susceptible tuberculosis (DS-TB) patients using LC-MS/MS and Ingenuity Pathway Analysis (IPA) to analyse the potential significance of these differentially expressed peptides. A total of 301 peptides were differentially expressed between MDR-TB and DS-TB groups. Of these, 24 and 16 peptides exhibited presented high (fold change ? 2.0, P < 0.05) and low (fold change ? -2.0, P < 0.05) levels in MDR-TB. Significant canonical pathways included the prothrombin activation system, coagulation system, and complement system. In the network of differentially expressed precursor proteins, lipopolysaccharide (LPS) regulates many precursor proteins, including four proteins correlated with organism survival. These four important differentially expressed proteins are prothrombin (F2), complement receptor type 2 (CR2), collagen alpha-2(V) chain (COL5A2), and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). After addition of CR2 peptide, IL-6 mRNA expression in THP-1 cells decreased significantly in dose- and time-dependent manners. Cumulatively, our study proposes potential biomarkers for MDR-TB diagnosis and enables a better understanding of the pathogenesis of MDR-TB. The functions of differentially expressed peptides, especially CR2, in MDR-TB require further investigation.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6354167 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Significance of the Differential Peptidome in Multidrug-Resistant Tuberculosis.

Yang Yan Y Wu Jianqing J

BioMed research international 20190117

Most multidrug-resistant tuberculosis (MDR-TB) patients fail to receive a timely diagnosis and treatment. Therefore, we explored the differentially expressed peptides in MDR-TB compared with drug-susceptible tuberculosis (DS-TB) patients using LC-MS/MS and Ingenuity Pathway Analysis (IPA) to analyse the potential significance of these differentially expressed peptides. A total of 301 peptides were differentially expressed between MDR-TB and DS-TB groups. Of these, 24 and 16 peptides exhibited pr ...[more]

PMID: 30792993

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Project description:BackgroundDespite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB.Methods and findingsWe developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of 720 dollars per QALY (8,700 dollars per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of 990 dollars per QALY (12,000 dollars per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of 11,000 dollars per QALY (160,000 dollars per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission.ConclusionsTreatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.

Dataset Information

Significance of the Differential Peptidome in Multidrug-Resistant Tuberculosis.

Publications

Significance of the Differential Peptidome in Multidrug-Resistant Tuberculosis.

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