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Corticosteroids and infliximab impair the performance of interferon-γ release assays used for diagnosis of latent tuberculosis
  1. Alexander Edwards1,
  2. Yifang Gao2,3,
  3. Raymond N Allan1,4,
  4. Darran Ball4,
  5. Hans de Graaf1,4,5,
  6. Tracy Coelho1,6,
  7. Vanessa Clifford7,
  8. Nigel Curtis7,
  9. Anthony Williams2,3,8,9,
  10. Saul N Faust1,4,10,11,
  11. Salah Mansour1,
  12. Ben Marshall1,10,12,
  13. Paul Elkington1,10,12,
  14. Marc Tebruegge1,7,10,11
  1. 1Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
  2. 2Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
  3. 3CRUK NIHR Southampton Experimental Cancer Medicine Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  4. 4NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  5. 5Department of Paediatric Rheumatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  6. 6Department of Paediatric Gastroenterology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  7. 7Department of Paediatrics, The University of Melbourne & Murdoch Children's Research Institute, Parkville, Australia
  8. 8Department of Immunology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  9. 9Wessex Investigational Sciences Hub, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  10. 10NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  11. 11Department of Paediatric Infectious Diseases & Immunology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  12. 12Department of Respiratory Medicine, University Hospital NHS Foundation Trust, Southampton, UK
  1. Correspondence to Dr Marc Tebruegge, NIHR Wellcome Trust Clinical Research Facility (Mailpoint 218), University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK; m.tebruegge{at}soton.ac.uk

Abstract

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.

  • Tuberculosis

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Footnotes

  • Twitter Follow Marc Tebruegge @ResearchTB

  • Contributors Study concept and design: AE, YG, RNA, VC, NC, AW, PE, and MT; participant recruitment: BM, PE, and MT; sample processing and analysis: AE, YG, DB, and MT; analysis of data: AE, YG, RNA, HdG, TC, VC, NC, PE, and MT; data interpretation and drafting of the manuscript: AE, VC, NC, SM, PE, and MT. All authors critically read, commented on, and approved the final version of the manuscript.

  • Funding HdG, DB, RNA and SNF are supported by the Southampton NIHR Wellcome Trust Clinical Research Facility; MT was supported by a Clinical Lectureship provided by the UK National Institute for Health Research.

  • Competing interests MT has received QuantiFERON-TB Gold assays at reduced cost for related research projects from the manufacturer (Cellestis/Qiagen). The manufacturer had no influence on the study design, data interpretation, writing of the manuscript or decision to submit the data for publication.

  • Ethics approval The study was approved by the National Research Ethics Service Committee South Central (approval number 13/SC/0043).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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