Title: Longitudinal analysis of host protein serum signatures of treatment and recovery in pulmonary tuberculosis

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. Serum that was collected at baseline and 8, 17, 26, and 52 weeks from 30 TB patients experiencing durable cure were evaluated and compared using a sensitive LC-MS/MS proteomic platform for the detection and quantification of differential host protein signatures relative to timepoint. The global proteome signature was analyzed for statistical differences across the time course and between disease severity and treatment groups. A total of 676 proteins showed differential expression in the serum over these timepoints relative to baseline. Comparisons to understand serum protein dynamics at 8 weeks, treatment endpoints at 17 and 26 weeks, and post-treatment at 52 weeks were performed. The largest protein abundance changes were observed at 8 weeks as the initial effects of antibiotic treatment strongly impacted inflammatory and immune modulated responses. However, the largest number of proteome changes was observed at the end of treatment time points 17 and 26 weeks respectively. Post-treatment 52-week results showed an abatement of differential proteome signatures from end of treatment, though interestinglymore » those proteins uniquely significant at post-treatment were almost exclusively downregulated. Patients were additionally stratified based upon disease severity and compared across all timepoints, identifying 461 discriminating proteome signatures. These proteome signatures collapsed into discrete expression profiles with distinct pathways across immune activation and signaling, hemostasis, and metabolism annotations. Insulin-like growth factor (IGF) and Integrin signaling maintained a severity signature through 52 weeks, implying an intrinsic disease severity signature well into the post-treatment timeframe. Previous proteome studies have primarily focused on the 8-week timepoint in relation to culture conversion status. While this study confirms previous observations, it also highlights some differences. The inclusion of additional end of treatment and post-treatment time points offers a more comprehensive assessment of treatment progression within the serum proteome. Examining the expression dynamics at these later time periods will help in the investigation of relapse patients and has provided indicative markers of response and recovery.« less

Authors:

Powell, Samantha M.  ^[1];

• Search DOE PAGES for author "Powell, Samantha M."
• Search DOE PAGES for ORCID "0000-0003-2670-0024"

Jarsberg, Leah G.  ^[2];

• Search DOE PAGES for author "Jarsberg, Leah G."
• Search DOE PAGES for ORCID "0000-0001-6548-6337"

Zionce, Erin M. ^[1]; Anderson, Lindsey N.  ^[1];

• Search DOE PAGES for author "Anderson, Lindsey N."
• Search DOE PAGES for ORCID "0000-0002-8741-7823"

Gritsenko, Marina A.  ^[1];

• Search DOE PAGES for author "Gritsenko, Marina A."
• Search DOE PAGES for ORCID "0000-0001-9992-9829"

Nahid, Payam ^[2]; Jacobs, Jon M.  ^[3]

• Search DOE PAGES for author "Jacobs, Jon M."
• Search DOE PAGES for ORCID "0000-0003-0557-7338"

---

+ Show Author Affiliations

1. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
2. University of California, San Francisco, CA (United States)
3. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)

Publication Date:

Thu Feb 29 00:00:00 EST 2024

Research Org.:

Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Org.:

USDOE Office of Science (SC); National Institutes of Health (NIH)

OSTI Identifier:

2322506

Report Number(s):

PNNL-SA-184858
Journal ID: ISSN 1932-6203

Grant/Contract Number:  

AC05-76RL01830; 1R01AI104589; 1R01AI127300

Resource Type:

Accepted Manuscript

Journal Name:

PLoS ONE

Additional Journal Information:

Journal Volume: 19; Journal Issue: 2; Journal ID: ISSN 1932-6203

Publisher:

Public Library of Science

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; tuberculosis; proteomes; serum proteins; extracellular matrix proteins; protein folding; hemostasis; protein abundance; protein expression