Population tailored modification of tuberculosis specific interferon-gamma release assay. Issue 2 (February 2016)

• Record Type: Journal Article
• Authors: Horvati, Kata; Bősze, Szilvia; Gideon, Hannah P.; Bacsa, Bernadett; Szabó, Tamás G.; Goliath, Rene; Rangaka, Molebogeng X.; Hudecz, Ferenc; Wilkinson, Robert J.; Wilkinson, Katalin A.
• Is Part Of: Journal of infection. Volume 72:Issue 2(2016)
• Page Start: 179
• Page End: 188
• Publication Date: 2016-02
• Subjects: Tuberculosis -- Interferon-Gamma Release Assays (IGRA) -- QuantiFERON assay -- Peptide epitope -- Rv2654c -- HIV; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2015.10.012
• Languages: English
• ISSNs: 0163-4453

Abstract

Summary: Objectives: 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 . Highlights: Refined epitope mapping of Rv2654c was performed in a South African Xhosa population. The most frequently recognized peptide is p51-65 (VRAVAESHGVAAVLF). Using p51-65 in the QFT assay resulted in a significant boosting effect. Peptide p51-65 can improve the population tailored detection of MTB sensitization.