Serum proteomics of active tuberculosis patients and contacts reveals unique processes activated during Mycobacterium tuberculosis infection

Jesús Mateos,Rajko Reljic,Isabel Medina,Tufária Mussá,Mónica Carrera,Ángeles Pallarés,Cremildo Gomes-Maueia,Artur Nguilichane,José M Gallardo,Luis Anibarro,África González-Fernández,Olivia Estévez

doi:10.1038/s41598-020-60753-5

Abstract

Tuberculosis (TB) is the most lethal infection among infectious diseases. The specific aim of this study was to establish panels of serum protein biomarkers representative of active TB patients and their household contacts who were either infected (LTBI) or uninfected (EMI-TB Discovery Cohort, Pontevedra Region, Spain). A TMT (Tamdem mass tags) 10plex-based quantitative proteomics study was performed in quintuplicate containing a total of 15 individual serum samples per group. Peptides were analyzed in an LC-Orbitrap Elite platform, and raw data were processed using Proteome Discoverer 2.1. A total of 418 proteins were quantified. The specific protein signature of active TB patients was characterized by an accumulation of proteins related to complement activation, inflammation and modulation of immune response and also by a decrease of a small subset of proteins, including apolipoprotein A and serotransferrin, indicating the importance of lipid transport and iron assimilation in the progression of the disease. This signature was verified by the targeted measurement of selected candidates in a second cohort (EMI-TB Verification Cohort, Maputo Region, Mozambique) by ELISA and nephelometry techniques. These findings will aid our understanding of the complex metabolic processes associated with TB progression from LTBI to active disease.

Highlights

Tuberculosis (TB) is the most lethal infection among infectious diseases
We focused on the analysis of nasal/oral fluid samples to obtain a deeper understanding of the innate immune processes implicated in resistance to the initial Mycobacterium tuberculosis (MTB) infection[27]
By analyzing serum samples of active TB patients and their contacts, our aim was to focus on the mechanisms activated systematically in the host during the progression of the disease

Summary

Introduction

Tuberculosis (TB) is the most lethal infection among infectious diseases. The specific aim of this study was to establish panels of serum protein biomarkers representative of active TB patients and their household contacts who were either infected (LTBI) or uninfected (EMI-TB Discovery Cohort, Pontevedra Region, Spain). The specific protein signature of active TB patients was characterized by an accumulation of proteins related to complement activation, inflammation and modulation of immune response and by a decrease of a small subset of proteins, including apolipoprotein A and serotransferrin, indicating the importance of lipid transport and iron assimilation in the progression of the disease. This signature was verified by the targeted measurement of selected candidates in a second cohort (EMI-TB Verification Cohort, Maputo Region, Mozambique) by ELISA and nephelometry techniques. In the present study our focus was on identifying the specific protein signatures in sera of active TB patients and their contacts, including latently infected (LTBI) and uninfected contacts

Objectives

Results

Conclusion