Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection

Dan Hameiri-Bowen; Evgeniya Sovershaeva; Trond Flaegstad; Tore Jarl Gutteberg; Lucky Gift Chiwiya Ngwira; Victoria Simms; Andrea M. Rehman; Grace McHugh; Tsitsi Bandason; Rashida Abbas Ferrand; Sarah Rowland-Jones; Louis Marie Yindom

doi:10.1097/qad.0000000000002964

Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection

Dan Hameiri-Bowen, Evgeniya Sovershaeva, Trond Flaegstad, Tore Jarl Gutteberg, Lucky Gift Chiwiya Ngwira, Victoria Simms, Andrea M. Rehman, Grace McHugh, Tsitsi Bandason, Rashida Abbas Ferrand, Sarah Rowland-Jones, Louis Marie Yindom

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

7 Citations (Scopus)

Abstract

OBJECTIVE

HIV-associated chronic lung disease (HCLD) is a common comorbidity in children and adolescents in sub-Saharan Africa (SSA). The pathogenesis of HCLD is unclear and may be driven by underlying dysregulated systemic immune activation and inflammation. We investigated the association between 26 plasma soluble biomarkers and HCLD.

DESIGN

Case--control analysis of baseline biomarker data from 336 children and adolescents (6-19 years old) with perinatal HIV infection (PHIV) and HCLD (cases) and 74 age-matched and sex-matched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z score less than -1 with no reversibility.

METHODS

Cryopreserved plasma collected at recruitment was used in a multiplex bead assay (Luminex) to measure baseline levels of soluble biomarkers. Logistic regression alongside data-reduction and techniques quantifying the interconnectedness of biomarkers were used to identify biomarkers associated with odds of HCLD.

RESULTS

Biomarkers of general immune activation and inflammation (β2M, CRP, sCCL5, GCSF, IFN-γ, IP-10), T-cell activation (sCD25, sCD27), platelet activation (sCD40-L), monocyte activation (sCD14), coagulation (D-Dimer), cellular adhesion (E-selectin), and extracellular matrix degradation (MMP-1, MMP-7, MMP-10) were associated with increased odds of HCLD. Exploratory PCA and assessment of biomarker interconnectedness identified T-cell and platelet activation as centrally important to this association.

CONCLUSION

HCLD was associated with a large number of soluble biomarkers representing a range of different pathways. Our findings suggest a prominent role for T-cell and platelet activation in HCLD.

Original language	English
Pages (from-to)	1743-1751
Number of pages	9
Journal	AIDS
Volume	35
Issue number	11
Early online date	15 Jun 2021
DOIs	https://doi.org/10.1097/qad.0000000000002964
Publication status	Published - 1 Sept 2021

Keywords

adolescents
Africa
biomarkers
HIV
lung disease
pathogenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/qad.0000000000002964

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Cite this

Hameiri-Bowen, D., Sovershaeva, E., Flaegstad, T., Gutteberg, T. J., Ngwira, L. G. C., Simms, V., Rehman, A. M., McHugh, G., Bandason, T., Ferrand, R. A., Rowland-Jones, S., & Yindom, L. M. (2021). Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection. AIDS, 35(11), 1743-1751. https://doi.org/10.1097/qad.0000000000002964

@article{a99cd68191b542f7bd8876a7326e4c05,

title = "Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection",

abstract = "OBJECTIVEHIV-associated chronic lung disease (HCLD) is a common comorbidity in children and adolescents in sub-Saharan Africa (SSA). The pathogenesis of HCLD is unclear and may be driven by underlying dysregulated systemic immune activation and inflammation. We investigated the association between 26 plasma soluble biomarkers and HCLD.DESIGNCase--control analysis of baseline biomarker data from 336 children and adolescents (6-19 years old) with perinatal HIV infection (PHIV) and HCLD (cases) and 74 age-matched and sex-matched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z score less than -1 with no reversibility.METHODSCryopreserved plasma collected at recruitment was used in a multiplex bead assay (Luminex) to measure baseline levels of soluble biomarkers. Logistic regression alongside data-reduction and techniques quantifying the interconnectedness of biomarkers were used to identify biomarkers associated with odds of HCLD.RESULTSBiomarkers of general immune activation and inflammation (β2M, CRP, sCCL5, GCSF, IFN-γ, IP-10), T-cell activation (sCD25, sCD27), platelet activation (sCD40-L), monocyte activation (sCD14), coagulation (D-Dimer), cellular adhesion (E-selectin), and extracellular matrix degradation (MMP-1, MMP-7, MMP-10) were associated with increased odds of HCLD. Exploratory PCA and assessment of biomarker interconnectedness identified T-cell and platelet activation as centrally important to this association.CONCLUSIONHCLD was associated with a large number of soluble biomarkers representing a range of different pathways. Our findings suggest a prominent role for T-cell and platelet activation in HCLD.",

keywords = "adolescents, Africa, biomarkers, HIV, lung disease, pathogenesis",

author = "Dan Hameiri-Bowen and Evgeniya Sovershaeva and Trond Flaegstad and Gutteberg, \{Tore Jarl\} and Ngwira, \{Lucky Gift Chiwiya\} and Victoria Simms and Rehman, \{Andrea M.\} and Grace McHugh and Tsitsi Bandason and Ferrand, \{Rashida Abbas\} and Sarah Rowland-Jones and Yindom, \{Louis Marie\}",

year = "2021",

month = sep,

day = "1",

doi = "10.1097/qad.0000000000002964",

language = "English",

volume = "35",

pages = "1743--1751",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

number = "11",

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Hameiri-Bowen, D, Sovershaeva, E, Flaegstad, T, Gutteberg, TJ, Ngwira, LGC, Simms, V, Rehman, AM, McHugh, G, Bandason, T, Ferrand, RA, Rowland-Jones, S & Yindom, LM 2021, 'Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection', AIDS, vol. 35, no. 11, pp. 1743-1751. https://doi.org/10.1097/qad.0000000000002964

TY - JOUR

T1 - Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection

AU - Hameiri-Bowen, Dan

AU - Sovershaeva, Evgeniya

AU - Flaegstad, Trond

AU - Gutteberg, Tore Jarl

AU - Ngwira, Lucky Gift Chiwiya

AU - Simms, Victoria

AU - Rehman, Andrea M.

AU - McHugh, Grace

AU - Bandason, Tsitsi

AU - Ferrand, Rashida Abbas

AU - Rowland-Jones, Sarah

AU - Yindom, Louis Marie

PY - 2021/9/1

Y1 - 2021/9/1

N2 - OBJECTIVEHIV-associated chronic lung disease (HCLD) is a common comorbidity in children and adolescents in sub-Saharan Africa (SSA). The pathogenesis of HCLD is unclear and may be driven by underlying dysregulated systemic immune activation and inflammation. We investigated the association between 26 plasma soluble biomarkers and HCLD.DESIGNCase--control analysis of baseline biomarker data from 336 children and adolescents (6-19 years old) with perinatal HIV infection (PHIV) and HCLD (cases) and 74 age-matched and sex-matched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z score less than -1 with no reversibility.METHODSCryopreserved plasma collected at recruitment was used in a multiplex bead assay (Luminex) to measure baseline levels of soluble biomarkers. Logistic regression alongside data-reduction and techniques quantifying the interconnectedness of biomarkers were used to identify biomarkers associated with odds of HCLD.RESULTSBiomarkers of general immune activation and inflammation (β2M, CRP, sCCL5, GCSF, IFN-γ, IP-10), T-cell activation (sCD25, sCD27), platelet activation (sCD40-L), monocyte activation (sCD14), coagulation (D-Dimer), cellular adhesion (E-selectin), and extracellular matrix degradation (MMP-1, MMP-7, MMP-10) were associated with increased odds of HCLD. Exploratory PCA and assessment of biomarker interconnectedness identified T-cell and platelet activation as centrally important to this association.CONCLUSIONHCLD was associated with a large number of soluble biomarkers representing a range of different pathways. Our findings suggest a prominent role for T-cell and platelet activation in HCLD.

AB - OBJECTIVEHIV-associated chronic lung disease (HCLD) is a common comorbidity in children and adolescents in sub-Saharan Africa (SSA). The pathogenesis of HCLD is unclear and may be driven by underlying dysregulated systemic immune activation and inflammation. We investigated the association between 26 plasma soluble biomarkers and HCLD.DESIGNCase--control analysis of baseline biomarker data from 336 children and adolescents (6-19 years old) with perinatal HIV infection (PHIV) and HCLD (cases) and 74 age-matched and sex-matched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z score less than -1 with no reversibility.METHODSCryopreserved plasma collected at recruitment was used in a multiplex bead assay (Luminex) to measure baseline levels of soluble biomarkers. Logistic regression alongside data-reduction and techniques quantifying the interconnectedness of biomarkers were used to identify biomarkers associated with odds of HCLD.RESULTSBiomarkers of general immune activation and inflammation (β2M, CRP, sCCL5, GCSF, IFN-γ, IP-10), T-cell activation (sCD25, sCD27), platelet activation (sCD40-L), monocyte activation (sCD14), coagulation (D-Dimer), cellular adhesion (E-selectin), and extracellular matrix degradation (MMP-1, MMP-7, MMP-10) were associated with increased odds of HCLD. Exploratory PCA and assessment of biomarker interconnectedness identified T-cell and platelet activation as centrally important to this association.CONCLUSIONHCLD was associated with a large number of soluble biomarkers representing a range of different pathways. Our findings suggest a prominent role for T-cell and platelet activation in HCLD.

KW - adolescents

KW - Africa

KW - biomarkers

KW - HIV

KW - lung disease

KW - pathogenesis

U2 - 10.1097/qad.0000000000002964

DO - 10.1097/qad.0000000000002964

M3 - Article

SN - 0269-9370

VL - 35

SP - 1743

EP - 1751

JO - AIDS

JF - AIDS

IS - 11

ER -

Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection

Abstract

Keywords

UN SDGs

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