Improving Assignments for Therapeutic and Prophylactic Treatment Within TB Households. A Potential for Immuno-Diagnosis?

• Published in: Frontiers in immunology Vol. 13; p. 801616
• Main Authors: Sivakumaran, Dhanasekaran, Jenum, Synne, Ritz, Christian, Vaz, Mario, Doherty, Timothy Mark, Grewal, Harleen M S
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17.03.2022
• Subjects: active TB; Biomarkers - analysis; cytokine and chemokines; Cytokines - analysis; Humans; Immunology; Mtb infection; Mycobacterium tuberculosis; preventive therapy; Prospective Studies; protein signature; soluble protein markers; Tuberculin Test; Tuberculosis - diagnosis; Tuberculosis - drug therapy; Tuberculosis - prevention & control; cytokine and chemokines; protein signature; Mtb infection; preventive therapy; active TB; soluble protein markers
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.801616

Delays in diagnosis and treatment of pulmonary tuberculosis (TB) can lead to more severe disease and increased transmission. Contact investigation among household contacts (HHCs) of TB patients is crucial to ensure optimal outcomes. In the context of a prospective cohort study in Palamaner, Southern India, this study attempted to assess the potential of 27 different soluble immune markers to accurately assign HHCs for appropriate treatment. A multiplex bead assay was applied on QuantiFERON (QFT)-nil supernatants collected from 89 HHCs grouped by longitudinal QFT status; ( ) infected (QFT positive at baseline and follow-up, n = 30), recent QFT converters (QFT-negative at baseline, n = 27) and converted to QFT-positivity within 6 months of exposure (at follow-up, n = 24) and QFT consistent negatives (n = 32). The 29 TB index cases represented Active TB. Active TB cases and HHCs with infection produced significantly different levels of both pro-inflammatory (IFNγ, IL17, IL8, IP10, MIP-1α, MIP1β, and VEGF) and anti-inflammatory (IL9 and IL1RA) cytokines. We identified a 4-protein signature (bFGF, IFNγ, IL9, and IP10) that correctly classified HHCs with infection vs. Active TB with a specificity of 92.6%, suggesting that this 4-protein signature has the potential to assign HHCs for either full-length TB treatment or preventive TB treatment. We further identified a 4-protein signature (bFGF, GCSF, IFNγ, and IL1RA) that differentiated HHCs with infection from QFT consistent negatives with a specificity of 62.5%, but not satisfactory to safely assign HHCs to no preventive TB treatment. QFT conversion, reflecting new infection, induced an elevated median concentration in nearly two-thirds (19/27) of the analyzed soluble markers compared to the levels measured at baseline. Validation in other studies is warranted in order to establish the potential of the immune biosignatures for optimized TB case detection and assignment to therapeutic and preventive treatment of infected individuals.