title: Lipoarabinomannan-specific TNF-α and IFN-γ as markers of protective immunity against tuberculosis: a cohort study in an endemic setting.
abstract: Lipoarabinomannan (LAM) is a virulent factor used for entry and survival of Mycobacterium tuberculosis (Mtb) in macrophages. Although the role of LAM for the diagnosis of tuberculosis (TB) has been extensively investigated, its cytokine response during natural Mtb infection in humans is largely unknown. In this study, LAM-specific IFN-γ, TNF-α, and IL-10 levels following whole blood assay were measured in untreated pulmonary TB patients, their contacts and community controls at baseline. In treated patients and contacts, cytokines were also measured at 6 and 12 months. At entry, 52.8% and 74.8% of controls and contacts were QFT-GIT positive, respectively. At baseline, untreated TB patients and contacts had significantly lower IFN-γ and TNF-α response compared to community controls (p < 0.0001). Besides, untreated patients had significantly higher TNF-α and IL-10 response compared to their contacts (p < 0.0001). At 6 months, contacts and treated TB patients had significantly increased INF-γ and TNF-α response (p < 0.0001). In TB patients, IFN-γ increased 10-fold following chemotherapy suggesting its potential role for treatment monitoring. The data suggests that LAM might have an anti-inflammatory effect during clinical TB and early Mtb infection. The data also suggests that LAM-induced IFN-γ and TNF-α could be used as biomarkers of protective immunity.
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.
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.
authors.forename: Adane
authors.initials: A
authors.lastname: Mihret
authors.affiliation: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors.forename: Yonas
authors.initials: Y
authors.lastname: Bekele
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: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005002:Ethiopia; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D000942:Antigens, Bacterial; D015415:Biomarkers; C508609:IL10 protein, human; D008070:Lipopolysaccharides; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C050016:lipoarabinomannan; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: IFN-γ; IL-10; Lipoarabinomannan; TNF-α; community controls; contacts; patients; tuberculosis