title: IFN-γ and IgA against non-methylated heparin-binding hemagglutinin as markers of protective immunity and latent tuberculosis: Results of a longitudinal study from an endemic setting.
abstract: BACKGROUND
  Heparin-binding hemagglutinin (HBHA) is a surface protein involved in epithelial attachment and extrapulmonary dissemination of Mycobacterium tuberculosis. HBHA is attracting increasing attention for its vaccine and diagnostic potential. In a longitudinal study, we investigated non-methylated, recombinant HBHA-specific cytokine and antibody profiles in cohorts of TB patients, their contacts and community controls in an endemic setting.
  
  
  METHODS
  Whole blood assay was done at baseline, 6 and 12 months in patients and contacts, and at entry in controls. ELISA was used to measure IFN-γ, TNF-α and IL-10 (from supernatants), and IgG, IgM and IgA (from sera).
  
  
  RESULTS
  Fifty-three percent of controls and 72.1% of contacts were QFT-GIT positive. Baseline IFN-γ was significantly higher in community controls and contacts compared to untreated TB patients (p < 0.0001). Controls had significantly higher IgA and lower IgM compared to both untreated TB patients and contacts (p < 0.0001). IL-10 was significantly higher in untreated TB patients compared to contacts and controls (p < 0.0001). In treated TB patients, IFN-γ significantly increased (p < 0.0001) whereas IL-10 significantly decreased (p < 0.001).
  
  
  CONCLUSIONS
  This study reports for the first time that anti-HBHA IgA could have the potential as a biomarker of protective immunity. In addition, non-methylated, recombinant HBHA-induced IFN-γ could be used as a biomarker of protective immunity and latent TB.
authors.affiliation: Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia; Department of Community Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway. Electronic address: mulg2002@yahoo.com.
authors.forename: Mulugeta
authors.initials: M
authors.lastname: Belay
authors.affiliation: Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Mengistu
authors.initials: M
authors.lastname: Legesse
authors.affiliation: Armauer Hansen Research Institute, Addis Ababa, Ethiopia; Department of Microbiology, Immunology and Parasitology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Adane
authors.initials: A
authors.lastname: Mihret
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Kees L
authors.initials: KL
authors.lastname: Franken
authors.affiliation: Department of Community Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Bjune
authors.affiliation: Department of Community Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway.
authors.forename: Fekadu
authors.initials: F
authors.lastname: Abebe
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007371:Interferon-gamma / Q000032:analysis*; D016753:Interleukin-10 / Q000032:analysis; D055985:Latent Tuberculosis / Q000276:immunology*; D037102:Lectins / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D015415:Biomarkers; D007070:Immunoglobulin A; D037102:Lectins; D014409:Tumor Necrosis Factor-alpha; C104578:heparin-binding hemagglutinin; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Community controls; Contacts; HBHA; IFN-γ; IL-10; IgA; IgG; IgM; Patients; Tuberculosis