Dataset Information

Proteomic analysis of peripheral blood mononuclear cells isolated from patients with pulmonary tuberculosis: a pilot study from Zanzibar, Tanzania

ABSTRACT: This study aimed at exploring the proteomic profile of PBMCs to predict response to treatment in pulmonary tuberculosis (PTB). This was a pilot study conducted among 8 adult patients from Zanzibar, Tanzania with confirmed PTB. Blood samples were collected at baseline, at 2 months of treatment, and at the end of 6 months of treatment. Proteins were extracted from PBMCs and analysed using LC‑MS/MS‑based label‑free quantitative proteomics. Overall, 3,530 proteins were quantified across the samples, and 12 differentially expressed proteins were identified at both 2 months of treatment and at treatment completion, which were involved in cellular and metabolic processes, as well as binding and catalytic activity. Seven were downregulated proteins (HSPA1B/HSPA1A, HSPH1, HSP90AA1, lipopolysaccharide binding protein, complement component 9, calcyclin-binding protein, and protein transport protein Sec31A), and 5 proteins were upregulated (SEC14 domain and spectrin repeat-containing protein 1, leucine-rich repeat-containing 8 VRAC subunit D, homogentisate 1,2-dioxygenase, NEDD8-activating enzyme E1 regulatory subunit, and N-acetylserotonin O-methyltransferase-like protein). The results showed that proteome analysis of PBMCs can be used as a novel technique to identify potential biomarkers to assess treatment efficacy in PTB. The novel proteins elucidated in this work may provide new insights for understanding PTB pathogenesis, treatment, and prognosis.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Tuberculosis

SUBMITTER: Even Birkeland

LAB HEAD: Tehmina Mustafa

PROVIDER: PXD029634 | Pride | 2023-03-11

REPOSITORIES: Pride

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Proteomic analysis of peripheral blood mononuclear cells isolated from patients with pulmonary tuberculosis: A pilot study from Zanzibar, Tanzania.

Barakat Ahmed A Birkeland Even E Jørstad Melissa D MD El Hajj Magalie M Marijani Msafiri M Døskeland Anne A Mjaavatten Olav O Berven Frode S FS Mustafa Tehmina T

PloS one 20230214 2

This study aimed at exploring the proteomic profile of PBMCs to predict treatment response in pulmonary tuberculosis (PTB). This was a pilot study conducted among 8 adult patients from Zanzibar, Tanzania with confirmed PTB. Blood samples were collected at baseline, at 2 months of treatment, and at the end of treatment at 6 months. Proteins were extracted from PBMCs and analyzed using LC-MS/MS based label free quantitative proteomics. Overall, 3,530 proteins were quantified across the samples, an ...[more]

PMID: 36787336

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Project description:The aim of the longitudinal analysis was to examine the transcriptional blood profile of active TB patients at the time of recruitment (before drug treatment) and then subsequently at specific time points after drug treatment to determine whether the signature is extinguished with treatment and when. Whole blood collected in tempus tubes from patients with different spectra of TB disease and healthy controls. All patients were sampled prior to the initiation of any antimycobacterial therapy. Active Pulmonary TB: PTB - All patients confirmed by isolation of Mycobacterium Tuberculosis on culture of sputum or bronchoalvelolar lavage fluid. Healthy controls - these were volunteers without exposure to TB who were negative by both tuberculin skin test (<15mm if BCG vaccinated, <6mm if unvaccinated); who were also negative by Interferon-Gamma Release assay(IGRA); specifically Quantiferon Gold In-Tube Assay (Cellestis, Australia). Here the aim of the experiment is to assess the longitudinal effect of antimycobacterial treatment on the active TB signature, during and after treatment. Blood was taken from the active TB patients at baseline, pre-treatment, 2 months after treatment inititation, and 12 months after treatment initiation, which would be after treatment was completed. These samples were then amplified at the same time with samples from healthy controls and hybridised to the same chips to permit an assessment of whether the post treatment samples had similar transcriptional profiles to healthy controls or were distinct. In this dataset: PTB baseline, n = 7; PTB 2 months, n = 7; PTB 12 months, n = 7. BCG+ control baseline, n =12. Experimental variables: Patient group: Active PTB; Healthy controls (all BCG vaccinated). ethnicity - a wide range of ethnic groups is represented. The active PTB group incorporates a range of smear positive and smear negative disease and a spectrum of disease extent/severity. Timepoint: 0 months = baseline pre-treatment;2 months = 2 months after initiation of treatment; 12 months = 12 months after initiation of treatment.

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