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The Usefulness of Serum CXCR3 Ligands for Evaluating the Early Treatment Response in Tuberculosis: A Longitudinal Cohort Study

Authors
Chung, WY; Yoon, D; Lee, KS; Jung, YJ; Kim, YS; Sheen, SS; Park, KJ
Citation
Medicine, 95(17):e3575-e3575, 2016
Journal Title
Medicine
ISSN
0025-79741536-5964
Abstract
Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB.We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-gamma and the CXCR3 ligands CXCL9 (monokine induced by IFN-gamma [MIG]), CXCL10 (IFN-gamma-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell alpha chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into "fast" and "slow" based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as "significant."In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P < 0.01) but did not decrease in the other groups. IFN-gamma levels showed no significant changes. The ability of significant decreases in marker levels to predict a fast response was evaluated. CXCL9 showed a sensitivity of 83%, and CXCL10 showed a specificity of 100%. Use of various combinations of CXCR3 ligands resulted in improvements in sensitivity (88%-93%), while specificity (92%-96%) was similar to that using single CXCR3 ligands. The decreases in CXCR3 ligand levels were less marked in the 2-month Mycobacterium tuberculosis culture-positive group than in the culture-negative group. There were significant differences in treatment outcomes in terms of 2-month culture positivity (P < 0.001), the significance of CXCL9 decreases (P < 0.01), and the significance of CXCL11 decreases (P < 0.05).In conclusion, CXCR3 ligands may be useful surrogate markers for the evaluation of early treatment response and showed utility as indicators of possible treatment failure in TB.
MeSH terms
AdultAntitubercular Agents/therapeutic use*Biomarkers/blood*Cohort StudiesFemaleFollow-Up StudiesHumansInterferon-gamma/bloodLongitudinal StudiesMaleMiddle AgedReceptors, CXCR3/blood*Republic of KoreaTreatment OutcomeTuberculosis, Pulmonary/drug therapy*
DOI
10.1097/MD.0000000000003575
PMID
27124069
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pulmonary & Critical Care Medicine
Journal Papers > School of Medicine / Graduate School of Medicine > Medical Informatics
Journal Papers > Research Organization > Institute for Medical Sciences
AJOU Authors
정, 우영윤, 덕용이, 규성정, 윤정김, 영선박, 광주
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