A Jayakumar1, E Vittinghoff2, M R Segal3, W R MacKenzie4, J L Johnson5, P Gitta6, J Saukkonen7, J Anderson8, M Weiner9, M Engle10, C Yoon11, M Kato-Maeda12, P Nahid13. 1. University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: archana.jayakumar@ucsf.edu. 2. University of California, San Francisco, 550 16th Street, 2nd Floor, San Francisco, CA 94158, USA. Electronic address: eric.vittinghoff@ucsf.edu. 3. University of California, San Francisco, 550 16th Street, 2nd Floor, San Francisco, CA 94158, USA. Electronic address: mark.segal@ucsf.edu. 4. Division of Tuberculosis Elimination, Centers for Disease Control & Prevention, 1600 Clifton Rd., NE MS E10, Atlanta, GA 30329, USA. Electronic address: wrm0@cdc.gov. 5. 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. 6. Uganda-Case Western Reserve University Research Collaboration, P.O. Box 663, Kampala, Uganda. Electronic address: pgitta@mucwru.or.ug. 7. Boston University School of Medicine, 150 South Huntington Avenue, Jamaica Plain, MA 02130, USA. Electronic address: jussi.saukkonen@va.gov. 8. University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: jilliananderson@gmail.com. 9. University of Texas Health Science Center, 7703 Floyd Curl., San Antonio, TX 78229, USA. Electronic address: weiner@uthscsa.edu. 10. University of Texas Health Science Center, 7703 Floyd Curl., San Antonio, TX 78229, USA. Electronic address: Englem2@uthscsa.edu. 11. University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: christina.yoon@ucsf.edu. 12. University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: midori.kato-maeda@ucsf.edu. 13. University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. Electronic address: pnahid@ucsf.edu.
Abstract
RATIONALE: 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). CONCLUSION: Exploratory post-hoc models including sTNF-R1, CRP, and age, classified 8 week culture status with promising accuracy.
RCT Entities:
RATIONALE: 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). CONCLUSION: Exploratory post-hoc models including sTNF-R1, CRP, and age, classified 8 week culture status with promising accuracy.
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