Serum proteomics of active tuberculosis patients and house hold contacts for the study of the processes activated during Mycobacterium tuberculosis infection

Abstract

Tuberculosis (TB) is the most lethal among the infectious diseases. The specific aim of our laboratory, as part of the Eliciting Mucosal immunity in Tuberculosis (EMI-TB) Horizon 2020 consortium (1), was to establish panels of serum protein biomarkers representative of active TB patients but also, if possible, of those individuals that have been in contact with a patient with microbiological confirmed pulmonary. Samples were collected from volunteer active tuberculosis patients (TB), and their infected (LTBI) and uninfected contacts (EMI-TB Discovery Cohort, Pontevedra Region, Spain). A TMT 10plex-based quantitative proteomics study was done in quintuplicate containing a total of 15 individual serum samples per group. Peptides were analyzed in a LC-Orbitrap Elite platform and raw data were processed using Proteome Discoverer 2.1 and R software. The specific protein signature of active TB patients is characterized by an accumulation of proteins related to complement activation, inflammation and modulation of immune response but 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 (2,3). This signature was verified by targeted measurement of selected candidates in a second cohort (EMI-TB Verification Cohort, Maputo Region, Mozambique) by ELISA and nephelometry techniques