Table_1_Improving Assignments for Therapeutic and Prophylactic Treatment Within TB Households. A Potential for Immuno-Diagnosis?.xlsx

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; M. tuberculosis (Mtb) 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 Mtb 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 Mtb 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 Mtb 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 Mtb 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 Mtb infected individuals.

肺结核（TB）的诊断与治疗延误可能导致病情加剧及传播风险增加。针对结核病患者家庭接触者（HHCs）的接触调查对于确保最佳治疗效果至关重要。在印度南部的帕拉曼纳进行的一项前瞻性队列研究中，本研究旨在评估27种不同的可溶性免疫标志物在准确分配HHCs以接受适当治疗方面的潜力。通过对89名按纵向QFT状态分组（QFT感染（QFT基线和随访均为阳性，n=30）、近期QFT转化者（QFT基线为阴性，n=27）及在暴露后6个月内转化为QFT阳性（随访时，n=24）和QFT持续阴性者，n=32）的家庭接触者采集的QuantiFERON（QFT）-nil上清液进行多重 bead 检测；29例TB索引病例代表活动性TB。活动性TB病例和M. tuberculosis（Mtb）感染者产生的促炎细胞因子（IFNγ、IL17、IL8、IP10、MIP-1α、MIP1β和VEGF）和抗炎细胞因子（IL9和IL1RA）水平存在显著差异。我们鉴定出一种四蛋白特征（bFGF、IFNγ、IL9和IP10），能够以92.6%的特异性正确分类Mtb感染者与活动性TB，表明这种四蛋白特征具有将HHCs分配至全长TB治疗或预防性TB治疗的潜力。此外，我们还鉴定出一种四蛋白特征（bFGF、GCSF、IFNγ和IL1RA），能够以62.5%的特异性将Mtb感染者与QFT持续阴性者区分开来，但不足以安全地将HHCs分配至无需预防性TB治疗。QFT转化，反映了新的Mtb感染，与基线水平相比，近三分之二（19/27）的分析可溶性标志物的中位浓度升高。为了确立免疫生物标志物在优化TB病例检测以及将Mtb感染者分配至治疗和预防治疗中的潜力，需要在其他研究中进行验证。