Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis.
New approaches to control the spread of tuberculosis (TB) are needed, including tools to predict development of active TB from latent TB infection (LTBI). Recent studies have described potential correlates of risk, in order to inform the development of prognostic tests for TB disease progression. These efforts have included unbiased approaches employing "omics" technologies, as well as more directed, hypothesis-driven approaches assessing a small set or even individual selected markers as candidate correlates of TB risk. Unbiased high-throughput screening of blood RNAseq profiles identified signatures of active TB risk in individuals with LTBI, ≥1 year before diagnosis. A recent infant vaccination study identified enhanced expression of T-cell activation markers as a correlate of risk prior to developing TB; conversely, high levels of Ag85A antibodies and high frequencies of interferon (IFN)-γ specific T-cells were associated with reduced risk of disease. Others have described CD27-IFN-γ+CD4+T-cells as possibly predictive markers of TB disease. T-cell responses to TB latency antigens, including heparin-binding haemagglutinin and DosR-regulon-encoded antigens have also been correlated with protection.Further studies are needed to determine whether correlates of risk can be used to prevent active TB through targeted prophylactic treatment, or to allow targeted enrolment into efficacy trials of new TB vaccines and therapeutic drugs.
Dept of Epidemiology and Preclinical Research, Translational Research Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
Elisa
E
Petruccioli
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa.|Division of Immunology, Dept of Pathology, University of Cape Town, Cape Town, South Africa.
Thomas J
TJ
Scriba
Dept of Epidemiology and Preclinical Research, Translational Research Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
Linda
L
Petrone
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa.|Division of Immunology, Dept of Pathology, University of Cape Town, Cape Town, South Africa.
Mark
M
Hatherill
Emerging Bacterial Pathogens Unit, Division of Immunology and Infectious Diseases, San Raffaele Scientific Institute, HSR, Milan, Italy.
Daniela M
DM
Cirillo
Leiden University Medical Center, Leiden, The Netherlands.
Simone A
SA
Joosten
Leiden University Medical Center, Leiden, The Netherlands.
Tom H
TH
Ottenhoff
Tuberculosis and Hepatitis Programme, FIND, Geneva, Switzerland.
Claudia M
CM
Denkinger
Dept of Epidemiology and Preclinical Research, Translational Research Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy delia.goletti@inmi.it.
Delia
D
Goletti
D000942:Antigens, Bacterial / Q000276:immunology; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D055985:Latent Tuberculosis / Q000097:blood* / Q000175:diagnosis*; D009169:Mycobacterium tuberculosis; D011237:Predictive Value of Tests
D000942:Antigens, Bacterial; D015415:Biomarkers; D007371:Interferon-gamma