Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children

Zhengzheng Zhang; Kerina Duri; Kevin L.W. Duisters; Johannes C. Schoeman; Panashe Chandiwana; Peter Lindenburg; Julia Jaeger; Susanne Ziegler; Marcus Altfeld; Isabelle Kohler; Amy Harms; Felicity Z. Gumbo; Thomas Hankemeier; Madeleine J. Bunders

doi:10.1097/QAD.0000000000003574

Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children

Zhengzheng Zhang, Kerina Duri, Kevin L.W. Duisters, Johannes C. Schoeman, Panashe Chandiwana, Peter Lindenburg, Julia Jaeger, Susanne Ziegler, Marcus Altfeld, Isabelle Kohler, Amy Harms, Felicity Z. Gumbo, Thomas Hankemeier, Madeleine J. Bunders^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

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Abstract

Objective:To determine immune-metabolic dysregulation in children born to women living with HIV.Methods:Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women with HIV (WHIV) and 12 uninfected women and their children up to 1.5 years of age were performed.Results:Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signalling lipids) and 24 immune mediators (e.g. cytokines) were quantified. combinational antiretroviral therapy (cART) exposure was categorized as cART initiation preconception (long), cART initiation postconception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HIV-exposed-uninfected (HEU)-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length.Conclusion:These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WHIV is associated with restricted infant growth.

Original language	English
Pages (from-to)	1367-1376
Number of pages	10
Journal	AIDS
Volume	37
Issue number	9
DOIs	https://doi.org/10.1097/QAD.0000000000003574
Publication status	Published - 15 Jul 2023

Bibliographical note

Funding Information:
The authors would like to thank the participants of the UZ-CHS birth cohort study and the research support team for their commitment including Dr G Kandawasvika, Dr P Kuona, Dr S Chimhuya (Paediatrics and Child Health Unit, Dr A Ziruma (Obstetrics and Gynaecology Unit), Mr Privilege Munjoma (Immunology Unit). Z.Z. would like to acknowledge the China Scholarship Council (CSC, no. 201608140084). The cohort is registered at www.clinicaltrials.gov.trial registration no.: NCT04087239.

Funding Information:
Funding: This work was supported by the Wellcome Trust under the University of Zimbabwe College of Health Sciences Southern Africa Consortium for Research Excellence (SACORE) [087537/F/08/A], the Deutsche Forschungsgemeinschaft (DFG) [BU 3630/2-1], and the Netherlands X-omics Initiative and NWO [184.034.019]. None of the funding bodies were be involved in the study design, data collection, data analysis, interpretation of findings and/ or manuscript writing.

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.

Keywords

combinational antiretroviral therapy
HIV-1
metabolism
paediatrics
vertical transmission

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altered_methionine_sulfone_levels_are_associated.4Final published version, 3.82 MBLicence: Article 25fa Dutch Copyright Act

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Zhang, Z., Duri, K., Duisters, K. L. W., Schoeman, J. C., Chandiwana, P., Lindenburg, P., Jaeger, J., Ziegler, S., Altfeld, M., Kohler, I., Harms, A., Gumbo, F. Z., Hankemeier, T., & Bunders, M. J. (2023). Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children. AIDS, 37(9), 1367-1376. https://doi.org/10.1097/QAD.0000000000003574

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title = "Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children",

abstract = "Objective:To determine immune-metabolic dysregulation in children born to women living with HIV.Methods:Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women with HIV (WHIV) and 12 uninfected women and their children up to 1.5 years of age were performed.Results:Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signalling lipids) and 24 immune mediators (e.g. cytokines) were quantified. combinational antiretroviral therapy (cART) exposure was categorized as cART initiation preconception (long), cART initiation postconception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HIV-exposed-uninfected (HEU)-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length.Conclusion:These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WHIV is associated with restricted infant growth.",

keywords = "combinational antiretroviral therapy, HIV-1, metabolism, paediatrics, vertical transmission",

author = "Zhengzheng Zhang and Kerina Duri and Duisters, {Kevin L.W.} and Schoeman, {Johannes C.} and Panashe Chandiwana and Peter Lindenburg and Julia Jaeger and Susanne Ziegler and Marcus Altfeld and Isabelle Kohler and Amy Harms and Gumbo, {Felicity Z.} and Thomas Hankemeier and Bunders, {Madeleine J.}",

note = "Funding Information: The authors would like to thank the participants of the UZ-CHS birth cohort study and the research support team for their commitment including Dr G Kandawasvika, Dr P Kuona, Dr S Chimhuya (Paediatrics and Child Health Unit, Dr A Ziruma (Obstetrics and Gynaecology Unit), Mr Privilege Munjoma (Immunology Unit). Z.Z. would like to acknowledge the China Scholarship Council (CSC, no. 201608140084). The cohort is registered at www.clinicaltrials.gov.trial registration no.: NCT04087239. Funding Information: Funding: This work was supported by the Wellcome Trust under the University of Zimbabwe College of Health Sciences Southern Africa Consortium for Research Excellence (SACORE) [087537/F/08/A], the Deutsche Forschungsgemeinschaft (DFG) [BU 3630/2-1], and the Netherlands X-omics Initiative and NWO [184.034.019]. None of the funding bodies were be involved in the study design, data collection, data analysis, interpretation of findings and/ or manuscript writing. Publisher Copyright: {\textcopyright} 2023 Lippincott Williams and Wilkins. All rights reserved.",

year = "2023",

month = jul,

day = "15",

doi = "10.1097/QAD.0000000000003574",

language = "English",

volume = "37",

pages = "1367--1376",

journal = "AIDS",

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TY - JOUR

T1 - Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children

AU - Zhang, Zhengzheng

AU - Duri, Kerina

AU - Duisters, Kevin L.W.

AU - Schoeman, Johannes C.

AU - Chandiwana, Panashe

AU - Lindenburg, Peter

AU - Jaeger, Julia

AU - Ziegler, Susanne

AU - Altfeld, Marcus

AU - Kohler, Isabelle

AU - Harms, Amy

AU - Gumbo, Felicity Z.

AU - Hankemeier, Thomas

AU - Bunders, Madeleine J.

N1 - Funding Information: The authors would like to thank the participants of the UZ-CHS birth cohort study and the research support team for their commitment including Dr G Kandawasvika, Dr P Kuona, Dr S Chimhuya (Paediatrics and Child Health Unit, Dr A Ziruma (Obstetrics and Gynaecology Unit), Mr Privilege Munjoma (Immunology Unit). Z.Z. would like to acknowledge the China Scholarship Council (CSC, no. 201608140084). The cohort is registered at www.clinicaltrials.gov.trial registration no.: NCT04087239. Funding Information: Funding: This work was supported by the Wellcome Trust under the University of Zimbabwe College of Health Sciences Southern Africa Consortium for Research Excellence (SACORE) [087537/F/08/A], the Deutsche Forschungsgemeinschaft (DFG) [BU 3630/2-1], and the Netherlands X-omics Initiative and NWO [184.034.019]. None of the funding bodies were be involved in the study design, data collection, data analysis, interpretation of findings and/ or manuscript writing. Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.

PY - 2023/7/15

Y1 - 2023/7/15

N2 - Objective:To determine immune-metabolic dysregulation in children born to women living with HIV.Methods:Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women with HIV (WHIV) and 12 uninfected women and their children up to 1.5 years of age were performed.Results:Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signalling lipids) and 24 immune mediators (e.g. cytokines) were quantified. combinational antiretroviral therapy (cART) exposure was categorized as cART initiation preconception (long), cART initiation postconception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HIV-exposed-uninfected (HEU)-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length.Conclusion:These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WHIV is associated with restricted infant growth.

AB - Objective:To determine immune-metabolic dysregulation in children born to women living with HIV.Methods:Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women with HIV (WHIV) and 12 uninfected women and their children up to 1.5 years of age were performed.Results:Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signalling lipids) and 24 immune mediators (e.g. cytokines) were quantified. combinational antiretroviral therapy (cART) exposure was categorized as cART initiation preconception (long), cART initiation postconception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HIV-exposed-uninfected (HEU)-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length.Conclusion:These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WHIV is associated with restricted infant growth.

KW - combinational antiretroviral therapy

KW - HIV-1

KW - metabolism

KW - paediatrics

KW - vertical transmission

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U2 - 10.1097/QAD.0000000000003574

DO - 10.1097/QAD.0000000000003574

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SN - 0269-9370

VL - 37

SP - 1367

EP - 1376

JO - AIDS

JF - AIDS

IS - 9

ER -

Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children

Abstract

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Keywords

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