Eva L Sudbury1, Vanessa Clifford2, Nicole L Messina3, Rinn Song4, Nigel Curtis5. 1. Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia. Electronic address: eva.sudbury@student.unimelb.edu.au. 2. Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia; Infectious Diseases Unit, The Royal Children's Hospital, Parkville, Australia. Electronic address: vanessa.clifford@rch.org.au. 3. Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia. Electronic address: nicole.messina@mcri.edu.au. 4. Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the National Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK; Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: rinn.song@paediatrics.ox.ac.uk. 5. Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital Melbourne, Parkville, Australia; Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia; Infectious Diseases Unit, The Royal Children's Hospital, Parkville, Australia. Electronic address: nigel.curtis@rch.org.au.
Abstract
OBJECTIVES: New tests are needed to overcome the limitations of existing immunodiagnostic tests for tuberculosis (TB) infection, including their inability to differentiate between active TB and latent TB infection (LTBI). This review aimed to identify the most promising cytokine biomarkers for use as stage-specific markers of TB infection. METHODS: A systematic review was done using electronic databases to identify studies that have investigated Mycobacterium tuberculosis (MTB)-specific cytokine responses as diagnostic tools to differentiate between LTBI and active TB. RESULTS: The 56 studies included in this systematic review measured the MTB-specific responses of 100 cytokines, the most frequently studied of which were IFN-γ, IL-2, TNF-α, IP-10, IL-10 and IL-13. Ten studies assessed combinations of cytokines, most commonly IL-2 and IFN-γ. For most cytokines, findings were heterogenous between studies. The variation in results likely relates to differences in the study design and laboratory methods, as well as participant and environmental factors. CONCLUSIONS: Although several cytokines show promise as stage-specific markers of TB infection, this review highlights the need for further well-designed studies, in both adult and paediatric populations, to establish which cytokine(s) will be of most use in a new generation of immunodiagnostic tests.
OBJECTIVES: New tests are needed to overcome the limitations of existing immunodiagnostic tests for tuberculosis (TB) infection, including their inability to differentiate between active TB and latent TB infection (LTBI). This review aimed to identify the most promising cytokine biomarkers for use as stage-specific markers of TB infection. METHODS: A systematic review was done using electronic databases to identify studies that have investigated Mycobacterium tuberculosis (MTB)-specific cytokine responses as diagnostic tools to differentiate between LTBI and active TB. RESULTS: The 56 studies included in this systematic review measured the MTB-specific responses of 100 cytokines, the most frequently studied of which were IFN-γ, IL-2, TNF-α, IP-10, IL-10 and IL-13. Ten studies assessed combinations of cytokines, most commonly IL-2 and IFN-γ. For most cytokines, findings were heterogenous between studies. The variation in results likely relates to differences in the study design and laboratory methods, as well as participant and environmental factors. CONCLUSIONS: Although several cytokines show promise as stage-specific markers of TB infection, this review highlights the need for further well-designed studies, in both adult and paediatric populations, to establish which cytokine(s) will be of most use in a new generation of immunodiagnostic tests.
Authors: Evangeline Ann Daniel; Balakumaran Sathiyamani; Kannan Thiruvengadam; Sandhya Vivekanandan; Hemanathan Vembuli; Luke Elizabeth Hanna Journal: Front Immunol Date: 2022-09-27 Impact factor: 8.786