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Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy

Nagu, T; Aboud, S; Rao, M; Matee, M; Axelsson, R; Valentini, D; Mugusi, F; ... Maeurer, M; + view all (2017) Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy. [Review]. International Journal of Infectious Diseases , 56 pp. 136-139. 10.1016/j.ijid.2017.01.022. Green open access

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Abstract

BACKGROUND: Intact immune responses to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) represent a biologically and clinically relevant correlate of ‘immunological fitness’ in humans. However, there is a lack of knowledge concerning anti-EBV or anti-CMV responses in patients with pulmonary tuberculosis (TB), in whom aberrant immune responses may promote progression of clinical disease. METHODS: Venous blood samples were obtained at the time of (sputum smear positive) pulmonary TB diagnosis. A whole blood assay was performed by exposing PBMCs (peripheral blood mononuclear cells) to a panel of infectious antigens, including CMV, EBV and mycobacterial proteins. Cell culture supernatants were collected after seven days and interferon gamma (IFN-γ) was measured using a sandwich ELISA. Patients received standard first line anti-tuberculosis rifampicin (R)/isoniazid (H)/ethambutol (E)/pyrazinamide (Z) for two months followed by RH for four months. RESULTS: PBMCs from cured patients (after treatment completion) exhibited significantly stronger IFN-γ responses to CMV (p=0.035), EBV (p=0.006) or Mycobacterium tuberculosis ESAT-6 (p = 0.043) at the time of diagnosis as compared to patients who succumbed to TB during treatment. IFN-γ responses to other viral (H5N1, HSV-1) as well as other mycobacterial (Ag85A, Rv2958c, Rv0447c) antigens were not found to be significantly different among patients who were cured or those who succumbed to TB. CONCLUSIONS: Increased cellular immune responses to CMV and EBV antigens at the time of diagnosis of pulmonary tuberculosis are associated with increased survival after a standard six months anti-TB therapy. CVM and EBV antigens may represent “intrinsic markers for immune fitness” and guide improved TB therapies including host-directed therapies.

Type: Article
Title: Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ijid.2017.01.022
Publisher version: http://doi.org/10.1016/j.ijid.2017.01.022
Language: English
Additional information: © 2017 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, pulmonary tuberculosis, EBV, CMV, cellular immune response, IFN-gamma, survival, TB therapy, HOST-DIRECTED THERAPIES, TUBERCULOSIS, ESAT-6
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/1551405
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