title: Host immunity to Mycobacterium tuberculosis and risk of tuberculosis: A longitudinal study among Greenlanders.
abstract: Human immune responses to latent Mycobacterium tuberculosis (Mtb) infection (LTBI) may enable individuals to control Mtb infection and halt progression to tuberculosis (TB), a hypothesis applied in several novel TB vaccines. We aimed to evaluate whether immune responses to selected LTBI antigens were associated with subsequent reduced risk of progression to TB.
  
  
  
  We conducted a population-based cohort study in East Greenland (2012-2014) including individuals aged 5-31years. A personal identifier allowed follow-up in national registers including the TB notification register. Mtb infection was defined by a positive Quantiferon test. Immune responses to LTBI antigens were assessed by whole blood antigen stimulation and interferon gamma measurement.
  
  
  
  Among 978 participants, 67 previously had TB. LTBI antigen (Rv1284, Rv2659, Rv2660c) immune response prevalence was 18%, 50%, 2% among Mtb-infected and 7%, 40%, 4% among non-infected (Quantiferon negative) participants. Among 911 participants without prior notified TB, 31 were notified with TB during study follow-up. Immune responses to LTBI antigens were not associated with reduced risk of subsequent TB; Rv1284 HR 0.92 (95%CI 0.28-3.04), Rv2659 HR 1.05 (95%CI 0.51-2.13), Rv2660c HR 3.06 (95%CI 0.70-13.37).
  
  
  
  In this large population-based study, human immune responses to selected LTBI antigens were not found to be strongly associated with reduced risk of subsequent TB.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Electronic address: swm@ssi.dk.
authors.forename: Sascha Wilk
authors.initials: SW
authors.lastname: Michelsen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Soborg
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Lars Jorge
authors.initials: LJ
authors.lastname: Diaz
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Soren Tetens
authors.initials: ST
authors.lastname: Hoff
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Koch
authors.affiliation: The Tasiilaq District Hospital, Postbox 510, GL-3913 Tasiilaq, Greenland.
authors.forename: Hans Christian Florian
authors.initials: HCF
authors.lastname: Sorensen
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Wohlfahrt
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D016021:Epidemiologic Studies; D005260:Female; D006116:Greenland / Q000453:epidemiology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D055985:Latent Tuberculosis / Q000453:epidemiology / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012307:Risk Factors; D014376:Tuberculosis / Q000453:epidemiology / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma
keywords: Antigens; Epidemiology; Immunity; Tuberculosis; Vaccines