title: High granulocyte/lymphocyte ratio and paucity of NKT cells defines TB disease in a TB-endemic setting.
abstract: Most people infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) actually maintain a strong immune response and are able to control bacterial growth (deemed latently infected (LTBI)), while approximately 10% progress to disease resulting in almost 2 million deaths per year. Determining the immune 'footprint' at specific stages of infection and disease will allow for better diagnostics, treatments and ultimately development of new vaccine candidates. In this study we performed multi-factorial flow cytometry on fresh blood from 56 TB cases, 46 Tuberculin Skin Test (TST) positive (LTBI) and 39 TST negative household contacts. We found a highly significant increase in granulocytes and decrease in B cells and invariant (Valpha24+Vbeta11+) NKT cells in TB cases compared to TST+ contacts (p<0.0001, p=0.007 and p=0.01 respectively) which were restored to LTBI levels following 6 months of TB treatment. Using support vector analysis, we found a combination of granulocyte and lymphocyte and/or NKT cell proportions allowed almost 90% correct classification into M. tuberculosis infection or disease. This work has important public health benefits in regards to diagnosis and treatment of TB in sub-Saharan Africa and in furthering our understanding of the requirements for protective immunity to TB.
authors.affiliation: Bacterial Diseases Programme, Medical Research Council Laboratories, PO Box 273, Banjul, The Gambia. jsutherland@mrc.gm
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Sutherland
authors.forename: David J
authors.initials: DJ
authors.lastname: Jeffries
authors.forename: Simon
authors.initials: S
authors.lastname: Donkor
authors.forename: Brigitte
authors.initials: B
authors.lastname: Walther
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hill
authors.forename: Ifedayo M O
authors.initials: IM
authors.lastname: Adetifa
authors.forename: Richard A
authors.initials: RA
authors.lastname: Adegbola
authors.forename: Martin O C
authors.initials: MO
authors.lastname: Ota
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D000942:Antigens, Bacterial / Q000276:immunology*; D058491:Bacterial Load; D015415:Biomarkers / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology*; D014374:Tuberculin Test; D014376:Tuberculosis / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D015415:Biomarkers; D007371:Interferon-gamma