Population tailored modification of tuberculosis specific interferon-gamma release assay

Horváti, Kata and Bősze, Szilvia and Gideon, Hannah P. and Bacsa, Bernadett and Szabó, Tamás G. and Goliath, Rene and Rangaka, Molebogeng X. and Hudecz, Ferenc and Wilkinson, Robert J. and Wilkinson, Katalin A. (2016) Population tailored modification of tuberculosis specific interferon-gamma release assay. Journal of Infection, 72 (2). pp. 179-188. ISSN 0163-4453

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Abstract

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 38e55 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 51e65. 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 0.30e7.35) to 2.83 (IQR 0.28e12.2; p Z 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 Z ns).

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