Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region.
<h4>Introduction</h4>Contemporary phase 2 TB disease treatment clinical trials have found that microbiologic treatment responses differ between African versus non-African regions, the reasons for which remain unclear. Understanding host and disease phenotypes that may vary by region is i...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0250586 |
| _version_ | 1818574336951320576 |
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| author | Leah G Jarsberg Komal Kedia Jason Wendler Aaron T Wright Paul D Piehowski Marina A Gritsenko Tujin Shi David M Lewinsohn George B Sigal Marc H Weiner Richard D Smith Joseph Keane Jon M Jacobs Payam Nahid |
| author_facet | Leah G Jarsberg Komal Kedia Jason Wendler Aaron T Wright Paul D Piehowski Marina A Gritsenko Tujin Shi David M Lewinsohn George B Sigal Marc H Weiner Richard D Smith Joseph Keane Jon M Jacobs Payam Nahid |
| author_sort | Leah G Jarsberg |
| collection | DOAJ |
| description | <h4>Introduction</h4>Contemporary phase 2 TB disease treatment clinical trials have found that microbiologic treatment responses differ between African versus non-African regions, the reasons for which remain unclear. Understanding host and disease phenotypes that may vary by region is important for optimizing curative treatments.<h4>Methods</h4>We characterized clinical features and the serum proteome of phase 2 TB clinical trial participants undergoing treatment for smear positive, culture-confirmed TB, comparing host serum protein expression in clinical trial participants enrolled in African and Non-African regions. Serum samples were collected from 289 participants enrolled in the Centers for Disease Control and Prevention TBTC Study 29 (NCT00694629) at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment).<h4>Results</h4>After a peptide level proteome analysis utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS) and subsequent statistical analysis, a total of 183 core proteins demonstrated significant differences at both baseline and at week 8 timepoints between participants enrolled from African and non-African regions. The majority of the differentially expressed proteins were upregulated in participants from the African region, and included acute phase proteins, mediators of inflammation, as well as coagulation and complement pathways. Downregulated proteins in the African population were primarily linked to nutritional status and lipid metabolism pathways.<h4>Conclusions</h4>We have identified differentially expressed nutrition and lipid pathway proteins by geographic region in TB patients undergoing treatment for pulmonary tuberculosis, which appear to be associated with differential treatment responses. Future TB clinical trials should collect expanded measures of nutritional status and further evaluate the relationship between nutrition and microbiologic treatment response. |
| first_indexed | 2024-12-15T00:25:15Z |
| format | Article |
| id | doaj.art-b9145d89909b47d4854d0bccdbebc6ef |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-15T00:25:15Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b9145d89909b47d4854d0bccdbebc6ef2022-12-21T22:42:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01165e025058610.1371/journal.pone.0250586Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region.Leah G JarsbergKomal KediaJason WendlerAaron T WrightPaul D PiehowskiMarina A GritsenkoTujin ShiDavid M LewinsohnGeorge B SigalMarc H WeinerRichard D SmithJoseph KeaneJon M JacobsPayam Nahid<h4>Introduction</h4>Contemporary phase 2 TB disease treatment clinical trials have found that microbiologic treatment responses differ between African versus non-African regions, the reasons for which remain unclear. Understanding host and disease phenotypes that may vary by region is important for optimizing curative treatments.<h4>Methods</h4>We characterized clinical features and the serum proteome of phase 2 TB clinical trial participants undergoing treatment for smear positive, culture-confirmed TB, comparing host serum protein expression in clinical trial participants enrolled in African and Non-African regions. Serum samples were collected from 289 participants enrolled in the Centers for Disease Control and Prevention TBTC Study 29 (NCT00694629) at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment).<h4>Results</h4>After a peptide level proteome analysis utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS) and subsequent statistical analysis, a total of 183 core proteins demonstrated significant differences at both baseline and at week 8 timepoints between participants enrolled from African and non-African regions. The majority of the differentially expressed proteins were upregulated in participants from the African region, and included acute phase proteins, mediators of inflammation, as well as coagulation and complement pathways. Downregulated proteins in the African population were primarily linked to nutritional status and lipid metabolism pathways.<h4>Conclusions</h4>We have identified differentially expressed nutrition and lipid pathway proteins by geographic region in TB patients undergoing treatment for pulmonary tuberculosis, which appear to be associated with differential treatment responses. Future TB clinical trials should collect expanded measures of nutritional status and further evaluate the relationship between nutrition and microbiologic treatment response.https://doi.org/10.1371/journal.pone.0250586 |
| spellingShingle | Leah G Jarsberg Komal Kedia Jason Wendler Aaron T Wright Paul D Piehowski Marina A Gritsenko Tujin Shi David M Lewinsohn George B Sigal Marc H Weiner Richard D Smith Joseph Keane Jon M Jacobs Payam Nahid Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region. PLoS ONE |
| title | Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region. |
| title_full | Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region. |
| title_fullStr | Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region. |
| title_full_unstemmed | Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region. |
| title_short | Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region. |
| title_sort | nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region |
| url | https://doi.org/10.1371/journal.pone.0250586 |
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