Plasma indoleamine 2,3-dioxygenase activity, a potential biomarker for tuberculosis

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Science Medicine Johannesburg, 2016 === Tuberculosis (TB) is a major global health challenge, especially in high HIV prevalence settings. To dat...

Full description

Bibliographic Details
Main Author: Adu-Gyamfi, Clement
Format: Others
Language:en
Published: 2016
Online Access:http://hdl.handle.net/10539/21530
id ndltd-netd.ac.za-oai-union.ndltd.org-wits-oai-wiredspace.wits.ac.za-10539-21530
record_format oai_dc
spelling ndltd-netd.ac.za-oai-union.ndltd.org-wits-oai-wiredspace.wits.ac.za-10539-215302019-05-11T03:40:34Z Plasma indoleamine 2,3-dioxygenase activity, a potential biomarker for tuberculosis Adu-Gyamfi, Clement A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Science Medicine Johannesburg, 2016 Tuberculosis (TB) is a major global health challenge, especially in high HIV prevalence settings. To date, however, there is no validated biomarker for diagnosing TB in HIV infected patients. Indoleamine 2, 3 dioxygenase (IDO) is an immunoregulatory enzyme capable of modulating cell mediated immunity (CMI). IDO catalyses the breakdown of tryptophan (Trp) to its toxic metabolites collectively known as kynurenines (Kyn). Elevated IDO activity has been proposed as a prognostic biomarker for TB, however, there is no longitudinal data to assess the clinical significance of elevated IDO activity in HIV-TB co-infection. We investigated whether IDO activity, as measured by Kyn-to-Trp ratio, using ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS) can act as a biomarker for diagnosing TB in HIV infected patients who develop active TB disease. Methodology Kyn and Trp concentrations were measured simultaneously using UPLC-MS/MS in the plasma of 32 HIV infected patients who developed active TB during a longitudinal study and compared with 70 control subjects, age and CD4 cell count matched, in the same HIV infected cohort who did not develop TB. Results IDO activity was significantly higher in TB patients than controls at the time of TB diagnosis (P = 0.0001). At 6 months prior to TB diagnosis, IDO activity was significantly higher in those who developed TB than controls (P = 0.0001). Within 6 months of anti-TB treatment, IDO activity in TB patients declined to almost same levels as that of the controls. To evaluate diagnostic significance of IDO activity using a receiver operating characteristic (ROC) curve, we selected 0.70 as the optimal cut-off. At time of TB diagnosis using both laboratory confirmed and clinical TB as gold standard, IDO activity gave a diagnostic sensitivity of 100% and a specificity of 98.5% with Positive and Negative predictive values of 96.9% and 100% for detecting active TB cases. Conclusion Our results, demonstrate the plausibility of increased IDO activity as a biomarker of active TB in HIV positive patients. Further, IDO activity may be a useful biomarker for predicting progress to active TB disease within 6 months or monitoring response to TB treatment. Strengths of the study include inclusion of an HIV infected control group and a longitudinal study design. MB2016 2016-12-14T10:57:45Z 2016-12-14T10:57:45Z 2016 Thesis http://hdl.handle.net/10539/21530 en application/pdf
collection NDLTD
language en
format Others
sources NDLTD
description A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Science Medicine Johannesburg, 2016 === Tuberculosis (TB) is a major global health challenge, especially in high HIV prevalence settings. To date, however, there is no validated biomarker for diagnosing TB in HIV infected patients. Indoleamine 2, 3 dioxygenase (IDO) is an immunoregulatory enzyme capable of modulating cell mediated immunity (CMI). IDO catalyses the breakdown of tryptophan (Trp) to its toxic metabolites collectively known as kynurenines (Kyn). Elevated IDO activity has been proposed as a prognostic biomarker for TB, however, there is no longitudinal data to assess the clinical significance of elevated IDO activity in HIV-TB co-infection. We investigated whether IDO activity, as measured by Kyn-to-Trp ratio, using ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS) can act as a biomarker for diagnosing TB in HIV infected patients who develop active TB disease. Methodology Kyn and Trp concentrations were measured simultaneously using UPLC-MS/MS in the plasma of 32 HIV infected patients who developed active TB during a longitudinal study and compared with 70 control subjects, age and CD4 cell count matched, in the same HIV infected cohort who did not develop TB. Results IDO activity was significantly higher in TB patients than controls at the time of TB diagnosis (P = 0.0001). At 6 months prior to TB diagnosis, IDO activity was significantly higher in those who developed TB than controls (P = 0.0001). Within 6 months of anti-TB treatment, IDO activity in TB patients declined to almost same levels as that of the controls. To evaluate diagnostic significance of IDO activity using a receiver operating characteristic (ROC) curve, we selected 0.70 as the optimal cut-off. At time of TB diagnosis using both laboratory confirmed and clinical TB as gold standard, IDO activity gave a diagnostic sensitivity of 100% and a specificity of 98.5% with Positive and Negative predictive values of 96.9% and 100% for detecting active TB cases. Conclusion Our results, demonstrate the plausibility of increased IDO activity as a biomarker of active TB in HIV positive patients. Further, IDO activity may be a useful biomarker for predicting progress to active TB disease within 6 months or monitoring response to TB treatment. Strengths of the study include inclusion of an HIV infected control group and a longitudinal study design. === MB2016
author Adu-Gyamfi, Clement
spellingShingle Adu-Gyamfi, Clement
Plasma indoleamine 2,3-dioxygenase activity, a potential biomarker for tuberculosis
author_facet Adu-Gyamfi, Clement
author_sort Adu-Gyamfi, Clement
title Plasma indoleamine 2,3-dioxygenase activity, a potential biomarker for tuberculosis
title_short Plasma indoleamine 2,3-dioxygenase activity, a potential biomarker for tuberculosis
title_full Plasma indoleamine 2,3-dioxygenase activity, a potential biomarker for tuberculosis
title_fullStr Plasma indoleamine 2,3-dioxygenase activity, a potential biomarker for tuberculosis
title_full_unstemmed Plasma indoleamine 2,3-dioxygenase activity, a potential biomarker for tuberculosis
title_sort plasma indoleamine 2,3-dioxygenase activity, a potential biomarker for tuberculosis
publishDate 2016
url http://hdl.handle.net/10539/21530
work_keys_str_mv AT adugyamficlement plasmaindoleamine23dioxygenaseactivityapotentialbiomarkerfortuberculosis
_version_ 1719081887812550656