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Longitudinal Analysis of Host Protein Serum Signatures of Treatment and Recovery in Pulmonary Tuberculosis

Samantha M. Powell, Leah G. Jarsberg, Erin L. M. Zionce, Lindsey N. Anderson, Marina A. Gritsenko, Payam Nahid, Jon M. Jacobs

Abstract

A better understanding of treatment progression and recovery in pulmonary tuberculosis (TB) infectious disease is crucial. This study analyzed longitudinal serum samples from pulmonary TB patients undergoing interventional treatment to identify surrogate markers for TB-related outcomes.

Introduction

Before COVID-19, tuberculosis (TB) was the leading cause of death from a single infectious agent [1, 2]. TB is widespread and the World Health Organization (WHO) estimates 25% of the world population is infected with TB and therefore represents a large burden on the world’s population and healthcare systems [2]. An estimated 10.6 million people fell ill with TB in 2021 according to the World Health Organization’s 2022 Global TB report, with increased cases and deaths attributed in part to disruptions in care caused by the COVID-19 pandemic [3]. The onset of the COVID-19 pandemic has created drastic setbacks, heightening the importance to refocus efforts on improving tools for prevention, diagnosis, and treatment of TB.

Materials and method

Written informed consent was obtained from all study participants for collection of serum for TB-related research. The institutional review board at University of California, San Francisco approved this biomarker study (UCSF IRB Number: 12–10360).

Results

A breakdown of the study is shown in Fig 1A and Table 1 details the clinical metadata of the 30 participants, whose serum at longitudinal collections 0, 8, 17, 26, and 52 weeks was used for this study. Utilizing a sensitive LC-MS based analytical platform, see Materials and methods for details, a total of 1889 proteins were identified and quantified across this patient sample set for further analysis (S1 Table in S1 File). Of the 1889 identified proteins, 676 had significant abundance differences as indicated by >90% coverage across all patients and time points as well as a measured p<0.05 for at least one time point comparison with baseline (week 0) (see Fig 1B and S2 Table in S1 File).

Discussion

The host response to treatment of acute pulmonary TB is a dynamic temporal process which we have investigated longitudinally through proteomic analysis of serum at specific timepoints. This complemented previous studies focused on early timepoints, i.e., 8 weeks of treatment, to correlate culture status with prospective serum markers of treatment efficacy/failure [11]. In this study, we moved beyond 8 weeks and captured the serum proteome signal at end of treatment, 17 and 26 weeks, and post treatment at 52 weeks. Each quantitative timepoint comparison provided insight into the mechanics of the proteome host response during each of these phases of treatment and recovery.

Acknowledgments

Work was performed in the Environmental Molecular Sciences Laboratory, a U. S. Department of Energy Office of Biological and Environmental Research national scientific user facility located at Pacific Northwest National Laboratory in Richland, Washington. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy under Contract No. DE-AC05-76RLO 1830. We are grateful to the MARK-TB Team for their engagement in biobanking and support of TB biomarker discovery research.

Citation: Powell SM, Jarsberg LG, Zionce ELM, Anderson LN, Gritsenko MA, Nahid P, et al. (2024) Longitudinal analysis of host protein serum signatures of treatment and recovery in pulmonary tuberculosis. PLoS ONE 19(2): e0294603. https://doi.org/10.1371/journal.pone.0294603

Editor: Suyan Tian, The First Hospital of Jilin University, CHINA

Received: June 30, 2023; Accepted: November 3, 2023; Published: February 29, 2024

Copyright: © 2024 Powell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD040546 and MassIVE Accession MSV000091392.

Funding: JMJ and PN acknowledge funding from the National Institutes of Health, National Institute of Allergy and Infectious Diseases 1R01AI104589 (TB Surrogate Markers for Assessing Response to Treatment) and 1R01AI127300 (Express 31 Study). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0294603#ack

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