Discrepancy between Mtb-specific IFN-γ and IgG responses in HIV-positive people with low CD4 counts

Maphe Mthembu; Kathryn A Bowman; Leela R L Davies; Sharon Khuzwayo; Lusanda Mazibuko; Thierry Bassett; Dirhona Ramjit; Zoey Mhlane; Farina Karim; Galit Alter; Thumbi Ndung'u; Emily B Wong

doi:10.1016/j.ebiom.2023.104504

Discrepancy between Mtb-specific IFN-γ and IgG responses in HIV-positive people with low CD4 counts

EBioMedicine. 2023 Apr:90:104504. doi: 10.1016/j.ebiom.2023.104504. Epub 2023 Mar 2.

Authors

Affiliations

¹ Africa Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Durban, South Africa.
² Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
³ Africa Health Research Institute, Durban, South Africa.
⁴ Africa Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Durban, South Africa; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; Division of Infection and Immunity, University College London, London, United Kingdom.
⁵ Africa Health Research Institute, Durban, South Africa; Division of Infectious Diseases, Heersink School of Medicine, University of Alabama at Birmingham, AL, USA. Electronic address: emily.wong@ahri.org.

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.

Keywords: CD4 count quartiles; HIV; Latent TB infection; QuantiFERON assay.

MeSH terms

Adult
Antibodies
CD4 Lymphocyte Count
HIV Infections* / complications
HIV Infections* / diagnosis
Humans
Interferon-gamma
Male
Mycobacterium tuberculosis*
South Africa / epidemiology
Tuberculosis* / diagnosis

Substances

Interferon-gamma
Antibodies

Grants and funding

T32 AI007387/AI/NIAID NIH HHS/United States