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Int J Infect Dis. 2017 Mar;56:136-139. doi: 10.1016/j.ijid.2017.01.022. Epub 2017 Feb 11.

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

Author information

1
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm and the Center for allogeneic stem cell transplantation (CAST), Karolinska University Hospital, Sweden; Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
2
Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
3
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm and the Center for allogeneic stem cell transplantation (CAST), Karolinska University Hospital, Sweden.
4
Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
5
Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, United Kingdom.
6
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm and the Center for allogeneic stem cell transplantation (CAST), Karolinska University Hospital, Sweden; Centre for Allogeneic Stem cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: markus.maeurer@ki.se.

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.

KEYWORDS:

CMV; EBV; IFN-γ; TB therapy,; cellular immune response; pulmonary tuberculosis; survival

PMID:
28193504
DOI:
10.1016/j.ijid.2017.01.022
[Indexed for MEDLINE]
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