Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region

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

doi:10.1371/journal.pone.0250586

Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region

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

Pulmonary and Critical Care Medicine

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Introduction 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. Methods 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). Results 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. Conclusions 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.

Original language	English (US)
Article number	e0250586
Journal	PloS one
Volume	16
Issue number	5 May
DOIs	https://doi.org/10.1371/journal.pone.0250586
State	Published - May 2021

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Jarsberg, L. G., Kedia, K., Wendler, J., Wright, A. T., Piehowski, P. D., Gritsenko, M. A., Shi, T., Lewinsohn, D. M., Sigal, G. B., Weiner, M. H., Smith, R. D., Keane, J., Jacobs, J. M., & Nahid, P. (2021). Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region. PloS one, 16(5 May), Article e0250586. https://doi.org/10.1371/journal.pone.0250586

Jarsberg, LG, Kedia, K, Wendler, J, Wright, AT, Piehowski, PD, Gritsenko, MA, Shi, T, Lewinsohn, DM, Sigal, GB, Weiner, MH, Smith, RD, Keane, J, Jacobs, JM & Nahid, P 2021, 'Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region', PloS one, vol. 16, no. 5 May, e0250586. https://doi.org/10.1371/journal.pone.0250586

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title = "Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region",

abstract = "Introduction 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. Methods 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). Results 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. Conclusions 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.",

author = "Jarsberg, {Leah G.} and Komal Kedia and Jason Wendler and Wright, {Aaron T.} and Piehowski, {Paul D.} and Gritsenko, {Marina A.} and Tujin Shi and Lewinsohn, {David M.} and Sigal, {George B.} and Weiner, {Marc H.} and Smith, {Richard D.} and Joseph Keane and Jacobs, {Jon M.} and Payam Nahid",

year = "2021",

month = may,

doi = "10.1371/journal.pone.0250586",

language = "English (US)",

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T1 - Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region

AU - Jarsberg, Leah G.

AU - Kedia, Komal

AU - Wendler, Jason

AU - Wright, Aaron T.

AU - Piehowski, Paul D.

AU - Gritsenko, Marina A.

AU - Shi, Tujin

AU - Lewinsohn, David M.

AU - Sigal, George B.

AU - Weiner, Marc H.

AU - Smith, Richard D.

AU - Keane, Joseph

AU - Jacobs, Jon M.

AU - Nahid, Payam

PY - 2021/5

Y1 - 2021/5

N2 - Introduction 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. Methods 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). Results 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. Conclusions 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.

AB - Introduction 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. Methods 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). Results 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. Conclusions 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.

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Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region

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