Frontiers in Immunology (Apr 2018)
A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts
- Fergal J. Duffy,
- Ethan Thompson,
- Katrina Downing,
- Sara Suliman,
- Harriet Mayanja-Kizza,
- Harriet Mayanja-Kizza,
- W. Henry Boom,
- Bonnie Thiel,
- January Weiner III,
- Stefan H. E. Kaufmann,
- Drew Dover,
- David L. Tabb,
- Hazel M. Dockrell,
- Tom H. M. Ottenhoff,
- Gerard Tromp,
- Thomas J. Scriba,
- Daniel E. Zak,
- Gerhard Walzl,
- the GC6-74 Consortium,
- S. H. E. Kaufmann,
- S. K. Parida,
- R. Golinski,
- J. Maertzdorf,
- J. Weiner,
- M. Jacobson,
- G. McEwen,
- G. Walzl,
- G. Black,
- G. van der Spuy,
- K. Stanley,
- M. Kriel,
- N. Du Plessis,
- N. Nene,
- A. Loxton,
- N. N. Chegou,
- S. Suliman,
- T. Scriba,
- H. Mahomed,
- M. Erasmus,
- O. Xasa,
- A. Veldsman,
- J. Hughes,
- K. Downing,
- A. Penn-Nicholson,
- H. Mulenga,
- B. Abel,
- M. Bowmaker,
- B. Kagina,
- W. Kwong C,
- W. Hanekom,
- T. H. M. Ottenhoff,
- M. R. Klein,
- M. C. Haks,
- K. L. Franken,
- A. Geluk,
- K. E. van Meijgaarden,
- S. A. Joosten,
- D. van Baarle,
- F. Miedema,
- W. H. Boom,
- B. Thiel,
- J. Sadoff,
- D. Sizemore,
- S. Ramachandran,
- L. Barker,
- M. Brennan,
- F. Weichold,
- S. Muller,
- L. Geiter,
- G. Schoolnik,
- G. Dolganov,
- T. Van,
- H. Mayanja-Kizza,
- M. Joloba,
- S. Zalwango,
- M. Nsereko,
- B. Okwera,
- H. Kisingo,
- H. Dockrell,
- S. Smith,
- P. Gorak-Stolinska,
- Y.-G. Hur,
- M. Lalor,
- J.-S. Lee,
- A. C. Crampin,
- N. French,
- B. Ngwira,
- A. B. Smith,
- K. Watkins,
- L. Ambrose,
- F. Simukonda,
- H. Mvula,
- F. Chilongo,
- J. Saul,
- K. Branson,
- D. Kassa,
- A. Abebe,
- T. Mesele,
- B. Tegbaru,
- R. Howe,
- A. Mihret,
- A. Aseffa,
- Y. Bekele,
- R. Iwnetu,
- M. Tafesse,
- L. Yamuah,
- M. Ota,
- J. Sutherland,
- P. Hill,
- R. Adegbola,
- T. Corrah,
- M. Antonio,
- T. Togun,
- I. Adetifa,
- S. Donkor,
- P. Andersen,
- I. Rosenkrands,
- M. Doherty,
- K. Weldingh
Affiliations
- Fergal J. Duffy
- The Center for Infectious Disease Research, Seattle, WA, United States
- Ethan Thompson
- The Center for Infectious Disease Research, Seattle, WA, United States
- Katrina Downing
- South African Tuberculosis Vaccine Initiative, Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Sara Suliman
- South African Tuberculosis Vaccine Initiative, Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Harriet Mayanja-Kizza
- Department of Medicine, Makerere University, Kampala, Uganda
- Harriet Mayanja-Kizza
- Department of Microbiology, Makerere University, Kampala, Uganda
- W. Henry Boom
- Case Western Reserve University, Cleveland, OH, United States
- Bonnie Thiel
- Case Western Reserve University, Cleveland, OH, United States
- January Weiner III
- Max Planck Institute for Infection Biology, Berlin, Germany
- Stefan H. E. Kaufmann
- Max Planck Institute for Infection Biology, Berlin, Germany
- Drew Dover
- The Center for Infectious Disease Research, Seattle, WA, United States
- David L. Tabb
- DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa
- Hazel M. Dockrell
- Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom
- Tom H. M. Ottenhoff
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
- Gerard Tromp
- DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa
- Thomas J. Scriba
- South African Tuberculosis Vaccine Initiative, Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Daniel E. Zak
- The Center for Infectious Disease Research, Seattle, WA, United States
- Gerhard Walzl
- DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa
- the GC6-74 Consortium
- S. H. E. Kaufmann
- S. K. Parida
- R. Golinski
- J. Maertzdorf
- J. Weiner
- M. Jacobson
- G. McEwen
- G. Walzl
- G. Black
- G. van der Spuy
- K. Stanley
- M. Kriel
- N. Du Plessis
- N. Nene
- A. Loxton
- N. N. Chegou
- S. Suliman
- T. Scriba
- H. Mahomed
- M. Erasmus
- O. Xasa
- A. Veldsman
- J. Hughes
- K. Downing
- A. Penn-Nicholson
- H. Mulenga
- B. Abel
- M. Bowmaker
- B. Kagina
- W. Kwong C
- W. Hanekom
- T. H. M. Ottenhoff
- M. R. Klein
- M. C. Haks
- K. L. Franken
- A. Geluk
- K. E. van Meijgaarden
- S. A. Joosten
- D. van Baarle
- F. Miedema
- W. H. Boom
- B. Thiel
- J. Sadoff
- D. Sizemore
- S. Ramachandran
- L. Barker
- M. Brennan
- F. Weichold
- S. Muller
- L. Geiter
- G. Schoolnik
- G. Dolganov
- T. Van
- H. Mayanja-Kizza
- M. Joloba
- S. Zalwango
- M. Nsereko
- B. Okwera
- H. Kisingo
- H. Dockrell
- S. Smith
- P. Gorak-Stolinska
- Y.-G. Hur
- M. Lalor
- J.-S. Lee
- A. C. Crampin
- N. French
- B. Ngwira
- A. B. Smith
- K. Watkins
- L. Ambrose
- F. Simukonda
- H. Mvula
- F. Chilongo
- J. Saul
- K. Branson
- D. Kassa
- A. Abebe
- T. Mesele
- B. Tegbaru
- R. Howe
- A. Mihret
- A. Aseffa
- Y. Bekele
- R. Iwnetu
- M. Tafesse
- L. Yamuah
- M. Ota
- J. Sutherland
- P. Hill
- R. Adegbola
- T. Corrah
- M. Antonio
- T. Togun
- I. Adetifa
- S. Donkor
- P. Andersen
- I. Rosenkrands
- M. Doherty
- K. Weldingh
- DOI
- https://doi.org/10.3389/fimmu.2018.00661
- Journal volume & issue
-
Vol. 9
Abstract
Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB)-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs) regulate the host response to MTB and circulating miRNAs (c-miRNAs) have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs) of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC) 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.
Keywords
