title: Population tailored modification of tuberculosis specific interferon-gamma release assay.
abstract: OBJECTIVE
  Blood-based Interferon-Gamma Release Assays (IGRA) identify Mycobacterium tuberculosis (MTB) sensitisation with increased specificity, but sensitivity remains impaired in human immunodeficiency virus (HIV) infected persons. The QuantiFERON-TB Gold In-Tube test contains peptide 38-55 of Rv2654c, based on data indicating differential recognition between tuberculosis patients and BCG vaccinated controls in Europe. We aimed to fine map the T cell response to Rv2654c with the view of improving sensitivity.
  
  
  METHODS
  Interferon-gamma ELISpot assay was used in HIV uninfected persons with latent and active tuberculosis to map peptide epitopes of Rv2654c. A modified IGRA was tested in two further groups of 55 HIV uninfected and 44 HIV infected persons, recruited in South Africa.
  
  
  RESULTS
  The most prominently recognised peptide was between amino acids 51-65. Using p51-65 to boost the QuantiFERON-TB Gold In-Tube assay, the quantitative performance of the modified IGRA increased from 1.83 IU/ml (IQR 0.30-7.35) to 2.83 (IQR 0.28-12.2; p = 0.002) in the HIV uninfected group. In the HIV infected cohort the percentage of positive responders increased from 57% to 64% but only after 3 months of ART (p = ns).
  
  
  CONCLUSIONS
  Our data shows the potential to population tailor detection of MTB sensitization using specific synthetic peptides and interferon-gamma release in vitro.
authors.affiliation: MTA-ELTE Research Group of Peptide Chemistry, Eötvös L. University, Budapest, Hungary.
authors.forename: Kata
authors.initials: K
authors.lastname: Horvati
authors.affiliation: MTA-ELTE Research Group of Peptide Chemistry, Eötvös L. University, Budapest, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Bősze
authors.affiliation: Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Gideon
authors.affiliation: MTA-ELTE Research Group of Peptide Chemistry, Eötvös L. University, Budapest, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Bacsa
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Tamás G
authors.initials: TG
authors.lastname: Szabó
authors.affiliation: Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Rene
authors.initials: R
authors.lastname: Goliath
authors.affiliation: Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Molebogeng X
authors.initials: MX
authors.lastname: Rangaka
authors.affiliation: MTA-ELTE Research Group of Peptide Chemistry, Eötvös L. University, Budapest, Hungary; Department of Organic Chemistry, Eötvös L. University, Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Hudecz
authors.affiliation: Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; The Francis Crick Institute Mill Hill Laboratory, London NW7 1AA, UK; Department of Medicine, Imperial College London W2 1PG, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.affiliation: Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; The Francis Crick Institute Mill Hill Laboratory, London NW7 1AA, UK. Electronic address: katalin.wilkinson@uct.ac.za.
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods*; D008297:Male; D012680:Sensitivity and Specificity; D013019:South Africa; D014376:Tuberculosis / Q000175:diagnosis*
chemical_list: D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; C483966:Rv2654 protein, Mycobacterium tuberculosis
keywords: HIV; Interferon-Gamma Release Assays (IGRA); Peptide epitope; QuantiFERON assay; Rv2654c; Tuberculosis