title: Serum biomarkers of treatment response within a randomized clinical trial for pulmonary tuberculosis.
abstract: BACKGROUND
  Biomarkers for monitoring response to anti-tuberculosis treatment are needed. We explored immune markers previously published as having predictive capability for 8 week culture status in 39 adults enrolled in a clinical trial in Kampala, Uganda.
  
  
  METHODS
  We consecutively selected 20 HIV-negative pulmonary TB subjects with positive cultures, and 19 subjects with negative cultures at the end of intensive phase therapy. At baseline and after 8 weeks, serum was assayed for nine cytokines and soluble cytokine receptors using multiplexed platforms or ELISA. We evaluated their association with week 8 culture status first using single-variable logistic models, then using cross-validated estimates of the C-statistic, a measure of discrimination, of candidate models including 2 or 3 analytes in addition to age.
  
  
  RESULTS
  All but one analyte decreased from baseline to week 8 (all p < 0.01). Individual biomarkers were not associated with 8 week culture status. Logistic models including increasing age, higher baseline soluble tumor necrosis factor receptor alpha 1 (sTNF-R1), and higher week 8 C-reactive protein (CRP) concentration classified subjects by culture status with up to 85% accuracy and acceptable discrimination (cross-validated C-statistic 0.76) and calibration (Hosmer-Lemeshow P > 0.2).
  
  
  CONCLUSIONS
  Exploratory post-hoc models including sTNF-R1, CRP, and age, classified 8 week culture status with promising accuracy.
authors.affiliation: University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: archana.jayakumar@ucsf.edu.
authors.forename: A
authors.initials: A
authors.lastname: Jayakumar
authors.affiliation: University of California, San Francisco, 550 16th Street, 2nd Floor, San Francisco, CA 94158, USA. Electronic address: eric.vittinghoff@ucsf.edu.
authors.forename: E
authors.initials: E
authors.lastname: Vittinghoff
authors.affiliation: University of California, San Francisco, 550 16th Street, 2nd Floor, San Francisco, CA 94158, USA. Electronic address: mark.segal@ucsf.edu.
authors.forename: M R
authors.initials: MR
authors.lastname: Segal
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control & Prevention, 1600 Clifton Rd., NE MS E10, Atlanta, GA 30329, USA. Electronic address: wrm0@cdc.gov.
authors.forename: W R
authors.initials: WR
authors.lastname: MacKenzie
authors.affiliation: Case Western Reserve University, University Hospitals Case Medical Center, 10900 Euclid Ave., Cleveland, OH 44106, USA; Uganda-Case Western Reserve University Research Collaboration, P.O. Box 663, Kampala, Uganda. Electronic address: jlj@case.edu.
authors.forename: J L
authors.initials: JL
authors.lastname: Johnson
authors.affiliation: Uganda-Case Western Reserve University Research Collaboration, P.O. Box 663, Kampala, Uganda. Electronic address: pgitta@mucwru.or.ug.
authors.forename: P
authors.initials: P
authors.lastname: Gitta
authors.affiliation: Boston University School of Medicine, 150 South Huntington Avenue, Jamaica Plain, MA 02130, USA. Electronic address: jussi.saukkonen@va.gov.
authors.forename: J
authors.initials: J
authors.lastname: Saukkonen
authors.affiliation: University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: jilliananderson@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.affiliation: University of Texas Health Science Center, 7703 Floyd Curl., San Antonio, TX 78229, USA. Electronic address: weiner@uthscsa.edu.
authors.forename: M
authors.initials: M
authors.lastname: Weiner
authors.affiliation: University of Texas Health Science Center, 7703 Floyd Curl., San Antonio, TX 78229, USA. Electronic address: Englem2@uthscsa.edu.
authors.forename: M
authors.initials: M
authors.lastname: Engle
authors.affiliation: University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: christina.yoon@ucsf.edu.
authors.forename: C
authors.initials: C
authors.lastname: Yoon
authors.affiliation: University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: midori.kato-maeda@ucsf.edu.
authors.forename: M
authors.initials: M
authors.lastname: Kato-Maeda
authors.affiliation: University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: pnahid@ucsf.edu.
authors.forename: P
authors.initials: P
authors.lastname: Nahid
mesh_terms: D000328:Adult; D000367:Age Factors; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*; D011237:Predictive Value of Tests; D018121:Receptors, Cytokine / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D014454:Uganda; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D016207:Cytokines; D018121:Receptors, Cytokine; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human; D002097:C-Reactive Protein
keywords: Biomarkers; Pulmonary; Treatment response; Tuberculosis