title: Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study.
abstract: 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.
authors.affiliation: From the Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, Taiwan (M-RL, L-YC, C-KL); Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (M-RL, L-YC, C-KL, J-YW, L-NL, C-JY); Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University (M-RL); Department of Internal Medicine, Taoyuan General Hospital, Taoyuan (C-JT, W-JW, T-YC); Department of Laboratory, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu (C-MY); Department of Traumatology (C-CS); and Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan (L-NL).
authors.forename: Meng-Rui
authors.initials: MR
authors.lastname: Lee
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Tsai
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Wang
authors.forename: Tzu-Yi
authors.initials: TY
authors.lastname: Chuang
authors.forename: Chih-Mann
authors.initials: CM
authors.lastname: Yang
authors.forename: Lih-Yu
authors.initials: LY
authors.lastname: Chang
authors.forename: Ching-Kai
authors.initials: CK
authors.lastname: Lin
authors.forename: Jann-Yuan
authors.initials: JY
authors.lastname: Wang
authors.forename: Chin-Chong
authors.initials: CC
authors.lastname: Shu
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Lee
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D018925:Chemokines / Q000097:blood*; D005260:Female; D053804:Granzymes / Q000097:blood*; D006801:Humans; D007378:Interleukins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D018925:Chemokines; D007378:Interleukins; D053804:Granzymes; D020784:Matrix Metalloproteinase 8