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Mass spectrometric identification of mycobacterium tuberculosis antigens in bronchoalveolar lavage fluid at the end of curative TB treatment.
Thesis (MSc)--Stellenbosch University, 2024.
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Stellenbosch : Stellenbosch University
2025
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| _version_ | 1867613826028929024 |
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| access_status_str | Open Access |
| author | Tenkeu, Sylvain Zemsi |
| author2 | Walzl, Gerhard |
| author_browse | Tenkeu, Sylvain Zemsi Walzl, Gerhard |
| author_facet | Walzl, Gerhard Tenkeu, Sylvain Zemsi |
| author_sort | Tenkeu, Sylvain Zemsi |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description |
Thesis (MSc)--Stellenbosch University, 2024. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/131928 |
| institution | Stellenbosch University (South Africa) |
| last_indexed | 2026-06-10T12:42:17.808Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/131928 Mass spectrometric identification of mycobacterium tuberculosis antigens in bronchoalveolar lavage fluid at the end of curative TB treatment. Tenkeu, Sylvain Zemsi Walzl, Gerhard Malherbe, Stephanus T. Bali, Sinazo Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Molecular Biology and Human Genetics. Mass spectrometry Mycobacterium tuberculosis Antigens Bronchoalveolar lavage UCTD Thesis (MSc)--Stellenbosch University, 2024. ENGLISH ABSTRACT: Background: Post Tuberculosis Lung Diseases or PTLD is defined as the presence of a chronic respiratory abnormality, with or without symptoms, attributable at least in part to previous tuberculosis. As of 2020, an estimated 155 million individuals worldwide survived Tuberculosis, and within this population evidence suggests a substantial burden of Post-Tuberculosis Lung Diseases (PTLD). There is a need to understand the mechanism underlying Post-Tuberculosis Lung Diseases (PTLD) to guide clinical management interventions. Ongoing inflammation in the lung may be one of the underlying mechanisms. Proteomics, an integrated research field centered around the identification and quantification of proteins in biological samples combined with mass spectrometry, could provide insights into the cause of this persistent inflammation. Objectives: To determine if Mycobacterium tuberculosis antigens are still present in the bronchoalveolar lavage fluid (BAL fluid) within the first 6 months following the completion of antituberculosis treatment, and if present, to establish their relationship with PET-CT scan lesions and functional test abnormalities. Methods: BAL fluid samples were collected from adults who had recently completed TB treatment within the past 6 months at Stellenbosch University-Immunology Research Group and South African Tuberculous Vaccine Initiative clinical research sites, as part of the Post-Function Study. Participants also underwent 18F-fluoorodeoxyglucose PET-CT (Positron Emission Tomography - Computerized Tomography) scans and spirometry. For the detection of Mycobacterium tuberculosis antigens in the BAL fluid, we employed Data Independent Acquisition (DIA) Liquid Chromatography Mass Spectrometry (LC-MS/MS). Results: We analysed the bronchoalveolar lavage fluid of 30 cured adult participants and 14 controls from the community. We detected the presence of six Mycobacterium tuberculosis antigens (A5TZ77, A5U7L9, A5TYA9, P9WLX5, A5U2V0, P9WJM1) distributed across 19 participants out of 30 participants (Figure 8). There was a positive correlation between the presence of the antigen P9WJM1, with the number of lobes affected (0.31; P=0.04), the total hard volume (0.17; P=0.007), and the total cavities (0.22; P=0.03), respectively. We found a significant change in the presence of the protein “A5TYA9” gene MRA_0401 depending on the time elapsed since the last treatment and there was no statistically significant correlation between the spirometry characteristics and the identified Mycobacterium tuberculosis antigens. Conclusion: Mycobacterium tuberculosis antigens are still present in BAL fluid after completion of antituberculosis treatment. The antigen P9WJM1 correlates with CT scan severity parameters, showing the potential relationship between the extent of disease and residual mycobacterial antigen presence. AFRIKAANSE OPSOMMING: Agtergrond: Post-tuberkulose-longsiekte, of PTLD, word gedefinieer as die teenwoordigheid van ‘n chroniese respiratoriese abnormaliteit, met of sonder simptome, wat ten minste gedeeltelik aan vorige tuberkulose infeksie toegeskryf kan word. Vanaf 2020 het 'n geraamde 155 miljoen individue wêreldwyd tuberkulose oorleef, en in hierdie bevolking dui bewyse op 'n betekenisvolle las geheg aan post-tuberkulose longsiektes (PTLD). Daar is 'n behoefte om die onderliggende meganisme van PTLD te verstaan om kliniese intervensies te lei. Voortdurende inflammasie in die long kan een van die onderliggende meganismes wees. Proteomics, 'n geïntegreerde navorsingsveld wat gesentreer is rondom die identifisering en kwantifisering van proteïene in biologiese monsters gekombineer met massaspektrometrie, kan insigte verskaf oor die oorsaak van hierdie aanhoudende inflammasie. Doelwitte: Om vas te stel of Mycobacterium tuberculosis antigene nog teenwoordig is in die brongoalveolêre spoelvloeistof (BAL vloeistof) binne die eerste 6 maande na die voltooiing van antituberkulose behandeling, en indien teenwoordig, om hul verband met PET-CT skandering letsels en funksionele toets abnormaliteite vas te stel. Metodes: BAL-vloeistofmonsters is ingesamel van volwassenes wat in die afgelope ses maande TBbehandeling voltooi het by SU-IRG en SATVI, as deel van die Post-Funksie studie. Deelnemers het ook PET-CT (Positron Emission Tomography - Computerized Tomography) skanderings, spirometrie en 6-minute looptoetse ondergaan. Vir die opsporing van Mycobacterium tuberculosis-antigene in die BAL-vloeistof het ons Data Independent Acquisition (DIA) Liquid Chromatography Mass Spectrometrie (LC-MS/MS) gebruik. Resultate: Ons het die brongoalveolêre spoelvloeistof van 30 geneesde volwasse deelnemers en 14 kontroles uit die gemeenskap ontleed. Ons het die teenwoordigheid van ses Mycobacterium tuberculosis antigene (A5TZ77, A5U7L9, A5TYA9, P9WLX5, A5U2V0, P9WJM1) oor 19 deelnemers uit 30 deelnemers versprei (Figuur 7) opgespoor. Daar was 'n positiewe korrelasie tussen die teenwoordigheid van die antigeen P9WJM1, met die aantal lobbe wat aangetas is https://scholar.sun.ac.za v (0.31; P=0.04), die totale harde volume (0.17; P=0.007) en die totale holtes (0.22; P=0.03) , onderskeidelik. Ons het 'n beduidende verandering in die teenwoordigheid van die proteïen "A5TYA9" geen MRA_0401 gevind, afhangende van die tyd wat verloop het sedert die laaste behandeling en daar was geen statisties beduidende korrelasie tussen die spirometrie eienskappe en die geïdentifiseerde Mycobacterium tuberculosis antigene nie. Afsluiting: Mycobacterium tuberculosis antigene is steeds teenwoordig in BAL vloeistof na voltooiing van antituberkulose behandeling. Die P9WJM1 antigeen korreleer met die omvang van residuele CT-skandering parameters. Masters 2025-04-29T08:20:13Z 2025-04-29T08:20:13Z 2024-12 Thesis https://scholar.sun.ac.za/handle/10019.1/131928 Stellenbosch University xiii, 82 pages ; illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Mass spectrometry Mycobacterium tuberculosis Antigens Bronchoalveolar lavage UCTD Tenkeu, Sylvain Zemsi Mass spectrometric identification of mycobacterium tuberculosis antigens in bronchoalveolar lavage fluid at the end of curative TB treatment. |
| title | Mass spectrometric identification of mycobacterium tuberculosis antigens in bronchoalveolar lavage fluid at the end of curative TB treatment. |
| title_full | Mass spectrometric identification of mycobacterium tuberculosis antigens in bronchoalveolar lavage fluid at the end of curative TB treatment. |
| title_fullStr | Mass spectrometric identification of mycobacterium tuberculosis antigens in bronchoalveolar lavage fluid at the end of curative TB treatment. |
| title_full_unstemmed | Mass spectrometric identification of mycobacterium tuberculosis antigens in bronchoalveolar lavage fluid at the end of curative TB treatment. |
| title_short | Mass spectrometric identification of mycobacterium tuberculosis antigens in bronchoalveolar lavage fluid at the end of curative TB treatment. |
| title_sort | mass spectrometric identification of mycobacterium tuberculosis antigens in bronchoalveolar lavage fluid at the end of curative tb treatment |
| topic | Mass spectrometry Mycobacterium tuberculosis Antigens Bronchoalveolar lavage UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/131928 |
| work_keys_str_mv | AT tenkeusylvainzemsi massspectrometricidentificationofmycobacteriumtuberculosisantigensinbronchoalveolarlavagefluidattheendofcurativetbtreatment |