Serological analysis reveals differential antibody responses between TB patients and latently infected individuals from the TB endemic country of Mozambique

Andy C Tran; Eugenia Boariu; María García-Bengoa; Mi-Young Kim; Emil Joseph Vergara; Tufária Mussá; Rajko Reljic

doi:10.3389/fmed.2023.1286785

Serological analysis reveals differential antibody responses between TB patients and latently infected individuals from the TB endemic country of Mozambique

Front Med (Lausanne). 2023 Oct 9:10:1286785. doi: 10.3389/fmed.2023.1286785. eCollection 2023.

Authors

Andy C Tran¹, Eugenia Boariu¹, María García-Bengoa^{2

3

4}, Mi-Young Kim¹, Emil Joseph Vergara¹, Tufária Mussá⁵, Rajko Reljic¹

Affiliations

¹ Institute for Infection and Immunity, St George's University of London, London, United Kingdom.
² Institute of Biochemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
³ Research Center for Emerging Infections and Zoonosis (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.
⁴ LIONEX Diagnostics and Therapeutics GmbH, Braunschweig, Germany.
⁵ Department of Microbiology, Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique.

Abstract

Serological antibody profiling of tuberculosis (TB) patients and household contacts with latent TB infection (LTBI) could identify risk indicators of disease progression, and potentially also serve as an easily accessible diagnostic tool to discriminate between these two stages of Mycobacterium tuberculosis (Mtb) infection. Yet, despite significant efforts over many decades, neither application has yet fully materialised, and this is at least in part due to inconsistent and varying antibody profiles from different TB endemic regions. In this study, we conducted a retrospective exploratory analysis of serum antibodies in a cohort of active TB patients (ATB) and their interferon-gamma release assay (IGRA) positive household contacts (LTBI), as well as healthy controls (HC) from Mozambique, a country with a high TB burden from the Sub-Saharan region. Using several Mtb antigens as well as crude preparations of culture filtrate proteins (CFP) from Mtb and Bacille Calmette Guérin (BCG), we report that the most discriminatory response for TB and LTBI was observed for serum IgA antibodies to the MPT64 antigen, followed by IgG antibodies to Ag85B and CFP, with ATB patients having significantly higher levels than LTBI or BCG-vaccinated healthy controls. Conversely, sera from LTBI individuals had higher levels of IgG antibodies to the HBHA antigen than ATB. While our sample size (n = 21 for ATB, 18 for LTBI and 17 for HC) was too small to fully evaluate the diagnostic potential of these differing serological profiles, our study however preliminarily indicated high level of sensitivity (95%) and specificity (97%) of an ELISA MPT64-IgA test for discriminating TB from LTBI and healthy controls, supporting the notion that it alone, or possibly in combination with other antigens such as Ag85B or CFP could lead to development of an easily accessible diagnostic tool for TB.

Keywords: LTBI (latent TB infection); antibodies; antigens; diagnostics; latent infection; serology; tuberculosis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the EC H2020 grant 643558 (The EMI-TB project).