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Journal Article Ppublish 11 citations

PubMed: 36870197 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 90:104504

Authors: 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

Affiliations

  • Africa Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Durban, South Africa.
  • Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Africa Health Research Institute, Durban, South Africa.
  • 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.
  • Africa Health Research Institute, Durban, South Africa; Division of Infectious Diseases, Heersink School of Medicine, University of Alabama at Birmingham, AL, USA.

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.

MeSH

Cd4 Lymphocyte Count, Interferon-Gamma, Antibodies, Biomedical Research, Sex, Diagnosis, Infections

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