Corticosteroids and infliximab impair the performance of interferon-γ release assays used for diagnosis of latent tuberculosis.
The impact of immunosuppression on interferon-γ release assays and novel cytokine biomarkers of TB infection, mycobacteria-specific IL-2, IP-10 and TNF-α responses was investigated in an ex vivo model. Cytokine responses in standard QuantiFERON-TB Gold in-Tube (QFT-GIT) assays were compared with duplicate assays containing dexamethasone or infliximab. Dexamethasone converted QFT-GIT results from positive to negative in 30% of participants. Antigen-stimulated interferon-γ, IL-2 and TNF-α responses were markedly reduced, but IP-10 responses were preserved. Infliximab caused QFT-GIT result conversion in up to 30% of participants and substantial reductions in all cytokine responses. Therefore, corticosteroids and anti-TNF-α agents significantly impair interferon-γ release assay performance. IP-10 may be a more robust TB biomarker than interferon-γ in patients receiving corticosteroids.
Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Alexander
A
Edwards
Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|CRUK NIHR Southampton Experimental Cancer Medicine Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Yifang
Y
Gao
Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Raymond N
RN
Allan
NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Darran
D
Ball
Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|Department of Paediatric Rheumatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Hans
H
de Graaf
Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|Department of Paediatric Gastroenterology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Tracy
T
Coelho
Department of Paediatrics, The University of Melbourne & Murdoch Children's Research Institute, Parkville, Australia.
Vanessa
V
Clifford
Department of Paediatrics, The University of Melbourne & Murdoch Children's Research Institute, Parkville, Australia.
Nigel
N
Curtis
Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|CRUK NIHR Southampton Experimental Cancer Medicine Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|Department of Immunology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|Wessex Investigational Sciences Hub, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Anthony
A
Williams
Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|Department of Paediatric Infectious Diseases & Immunology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Saul N
SN
Faust
Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Salah
S
Mansour
Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|Department of Respiratory Medicine, University Hospital NHS Foundation Trust, Southampton, UK.
Ben
B
Marshall
Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|Department of Respiratory Medicine, University Hospital NHS Foundation Trust, Southampton, UK.
Paul
P
Elkington
Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|Department of Paediatrics, The University of Melbourne & Murdoch Children's Research Institute, Parkville, Australia.|NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.|Department of Paediatric Infectious Diseases & Immunology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Marc
0000-0003-4007-0807
M
Tebruegge
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D059425:Interferon-gamma Release Tests; D007376:Interleukin-2 / Q000378:metabolism; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D018501:Antirheumatic Agents; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; D000069285:Infliximab
Tuberculosis