Defining Discriminatory Antibody Fingerprints in Active and Latent Tuberculosis

• Type of Material: Article
• Authors: Nadege Nziza, Massachusetts Institute of Technology (MIT) and Harvard, Cambridge; Deniz Cizmeci, Massachusetts Institute of Technology (MIT) and Harvard, Cambridge; Leela Davies, Massachusetts Institute of Technology (MIT) and Harvard, Cambridge; Edward B Irvine, Massachusetts Institute of Technology (MIT) and Harvard, Cambridge; Wonyeong Jung, Massachusetts Institute of Technology (MIT) and Harvard, Cambridge; Brooke A Fenderson, Massachusetts Institute of Technology (MIT) and Harvard, Cambridge; Marwoi de Kock, University of Cape Town; Willem A Hanekom, Africa Health Research Institute, Durban; Kees LMC Franken, Leiden University; Cheryl Day, Emory University; Tom HM Ottenhoff, Leiden University; Galit Alter, Massachusetts Institute of Technology (MIT) and Harvard, Cambridge
• Language: English
• Date: 2022-04-20
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Nziza, Cizmeci, Davies, Irvine, Jung, Fenderson, de Kock, Hanekom, Franken, Day, Ottenhoff and Alter
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fimmu.2022.856906
• Title of Journal or Parent Work: FRONTIERS IN IMMUNOLOGY
• Volume: 13
• Start Page: 856906
• End Page: 856906
• Grant/Funding Information: We acknowledge the Gates Foundation (OPP1159416, OPP1151840, OPP1156795) and the NIH (1R561AI155149, the IMPACTB Consortium, and 3R37AI080289-11S1).
• Keywords: DIAGNOSIS; Immunology; antibodies; Science & Technology; ANTIGEN; biomarkers; HIV; active and latent tuberculosis; MYCOBACTERIUM-TUBERCULOSIS; FC ARRAY; IGG; T-CELLS; INFECTION; diagnostics; PULMONARY; HUMORAL IMMUNITY; Life Sciences & Biomedicine; B-CELLS
• Research Categories: Health Sciences, Public Health; Health Sciences, Immunology; Biology, Microbiology

Abstract

Tuberculosis (TB) is among the leading causes of death worldwide from a single infectious agent, second only to COVID-19 in 2020. TB is caused by infection with Mycobacterium tuberculosis (Mtb), that results either in a latent or active form of disease, the latter associated with Mtb spread. In the absence of an effective vaccine, epidemiologic modeling suggests that aggressive treatment of individuals with active TB (ATB) may curb spread. Yet, clinical discrimination between latent (LTB) and ATB remains a challenge. While antibodies are widely used to diagnose many infections, the utility of antibody-based tests to diagnose ATB has only regained significant traction recently. Specifically, recent interest in the humoral immune response to TB has pointed to potential differences in both targeted antigens and antibody features that can discriminate latent and active TB. Here we aimed to integrate these observations and broadly profile the humoral immune response across individuals with LTB or ATB, with and without HIV co-infection, to define the most discriminatory humoral properties and diagnose TB disease more easily. Using 209 Mtb antigens, striking differences in antigen-recognition were observed across latently and actively infected individuals that was modulated by HIV serostatus. However, ATB and LTB could be discriminated, irrespective of HIV-status, based on a combination of both antibody levels and Fc receptor-binding characteristics targeting both well characterized (like lipoarabinomannan, 38 kDa or antigen 85) but also novel Mtb antigens (including Rv1792, Rv1528, Rv2435C or Rv1508). These data reveal new Mtb-specific immunologic markers that can improve the classification of ATB versus LTB.