Mthembu, M;
Bowman, KA;
Davies, LRL;
Khuzwayo, S;
Mazibuko, L;
Bassett, T;
Ramjit, D;
... Wong, EB; + view all
(2023)
Discrepancy between Mtb-specific IFN-γ and IgG responses in HIV-positive people with low CD4 counts.
eBioMedicine
, 90
, Article 104504. 10.1016/j.ebiom.2023.104504.
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Abstract
Background: Tuberculosis (TB) is a leading infectious cause of death worldwide and treating latent TB infection (LTBI) with TB preventative therapy is a global priority. This study aimed to measure interferon gamma (IFN-γ) release assay (IGRA) positivity (the current reference standard for LTBI diagnosis) and Mtb-specific IgG antibodies in otherwise healthy adults without HIV and those living with HIV (PLWH). Methods: One-hundred and eighteen adults (65 without HIV and 53 antiretroviral-naïve PLWH), from a peri-urban setting in KwaZulu-Natal, South Africa were enrolled. IFN-γ released following stimulation with ESAT-6/CFP-10 peptides and plasma IgG antibodies specific for multiple Mtb antigens were measured using the QuantiFERON-TB Gold Plus (QFT) and customized Luminex assays, respectively. The relationships between QFT status, relative concentrations of anti-Mtb IgG, HIV-status, sex, age and CD4 count were analysed. Findings: Older age, male sex and higher CD4 count were independently associated with QFT positivity (p = 0.045, 0.05 and 0.002 respectively). There was no difference in QFT status between people with and without HIV infection (58% and 65% respectively, p = 0.06), but within CD4 count quartiles, people with HIV had higher QFT positivity than people without HIV (p = 0.008 (2nd quartile), <0.0001 (3rd quartile)). Concentrations of Mtb-specific IFN-γ were lowest, and relative concentrations of Mtb-specific IgGs were highest in PLWH in the lowest CD4 quartile. Interpretation: These results suggest that the QFT assay underestimates LTBI among immunosuppressed people with HIV and Mtb-specific IgG may be a useful alternative biomarker for Mtb infection. Further evaluation of how Mtb-specific antibodies can be leveraged to improve LTBI diagnosis is warranted, particularly in HIV-endemic areas. Fundings: NIH, AHRI, SHIP: SA-MRC and SANTHE.
| Type: | Article |
|---|---|
| Title: | Discrepancy between Mtb-specific IFN-γ and IgG responses in HIV-positive people with low CD4 counts |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ebiom.2023.104504 |
| Publisher version: | https://doi.org/10.1016/j.ebiom.2023.104504 |
| Language: | English |
| Additional information: | Copyright © 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | CD4 count quartiles, HIV, Latent TB infection, QuantiFERON assay |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10167701 |
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