880. Investigation of Plasma IP-10 During Treatment of Pulmonary Tuberculosis
Session: Poster Abstract Session: Bacterial Infections: Pathogenesis and Immunity
Friday, October 9, 2015
Room: Poster Hall
Background: : Monitoring response to anti-tuberculosis treatment (ATT) in patients with pulmonary tuberculosis (PTB) requires detection of Mycobacterium tuberculosis(Mtb) in sputum. However, current methods are suboptimal due to the poor performance of the sputum smear test and the long duration (3-6 weeks) required for culturing Mtb. We hypothesized that plamsa levels of Interferon-induced Protein-10 (IP-10), a chemokine secreted primarily by monocytes, would decrease with ATT and may be useful a plasma biomarker of ATT. While plasma-based soluble markers are not pathogen specific, they can be easily and affordably measured by Enzyme-Linked Immunosorbent Assays (ELISAs) and could complement sputum-based assessments. We sought to measure the levels of IP-10 in the plasma of patients with PTB, before, during and after completion of ATT. 

Methods: Human immunodeficiency virus negative subjects with smear-positive drug-susceptible PTB were enrolled prior to initiation of ATT at the Grady Memorial Hospital, Atlanta, GA and followed longitudinally during ATT. ATT was provided according to national guidelines. Blood samples were obtained at baseline and during ATT. Peripheral blood mononuclear cells (PBMC) and plasma were isolated for each patient at each time point. Plasma IP-10 levels were measured by ELISA.

Results: All patients achieved sputum culture-conversion and were considered cured. In plasma samples for four patients tested to date, IP-10 levels decreased with ATT. The decrease in IP-10 mirrored decreases in frequencies of CD38+, HLA-DR+, and Ki-67+ M. tuberculosis-specific CD4+IFN-γ+ T cells. These markers of T cell activation and proliferation were previously shown by our group to be biomarkers of treatment response.

Conclusion: In our limited sample set, the trend of decreasing plasma IP-10 during ATT appears to mirror the decrease in M. tuberculosis specific T cell markers of treatment response.

Marcos C. Schechter, MD1, Chris C. Ibegbu, PhD2,3, Toidi Adekambi, PhD2, Stephanie Cagle, BSMT1, Susan M. Ray, MD1 and Jyothi Rengarajan, PhD1,2, (1)Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, (2)Department of Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, (3)Yerkes National Primate Center, Department of Microbiology and Immunology, Emory University, Atlanta, GA

Disclosures:

M. C. Schechter, None

C. C. Ibegbu, None

T. Adekambi, None

S. Cagle, None

S. M. Ray, None

J. Rengarajan, None

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