Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy
Copyright © 2017. Published by Elsevier Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
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| Enthalten in: |
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases - 56(2017) vom: 05. März, Seite 136-139 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nagu, Tumaini [VerfasserIn] |
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| Links: |
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| Themen: |
Antitubercular Agents |
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| Anmerkungen: |
Date Completed 28.08.2017 Date Revised 02.12.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijid.2017.01.022 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM268920060 |
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| 100 | 1 | |a Nagu, Tumaini |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy |
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| 500 | |a Date Completed 28.08.2017 | ||
| 500 | |a Date Revised 02.12.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017. Published by Elsevier Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CMV | |
| 650 | 4 | |a EBV | |
| 650 | 4 | |a IFN-γ | |
| 650 | 4 | |a TB therapy, | |
| 650 | 4 | |a cellular immune response | |
| 650 | 4 | |a pulmonary tuberculosis | |
| 650 | 4 | |a survival | |
| 650 | 7 | |a Antitubercular Agents |2 NLM | |
| 650 | 7 | |a Tuberculosis Vaccines |2 NLM | |
| 700 | 1 | |a Aboud, Said |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Matee, Mecky |e verfasserin |4 aut | |
| 700 | 1 | |a Axelsson, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Valentini, Davide |e verfasserin |4 aut | |
| 700 | 1 | |a Mugusi, Ferdinand |e verfasserin |4 aut | |
| 700 | 1 | |a Zumla, Alimuddin |e verfasserin |4 aut | |
| 700 | 1 | |a Maeurer, Markus |e verfasserin |4 aut | |
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