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

Hameiri-Bowen, Dan, Sovershaeva, Evgeniya, Flaegstad, Trond, Gutteberg, Tore Jarl, Ngwira, Lucky-Gift, Simms, Victoria, Rehman, Andrea M, Mchugh, Grace, Bandason, Tsitsi, Ferrand, Rashida Abbas, Rowland-Jones, Sarah and Yindom, Louis-Marie (2021) 'Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection'. AIDS, Vol 35, Issue 11, pp. 1743-1751.

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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.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WF Respiratory System > Lungs > WF 600 Lungs WS Pediatrics > Diseases of Children and Adolescents > By System > WS 280 Respiratory system
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1097/QAD.0000000000002964
Depositing User:	Julie Franco
Date Deposited:	19 Aug 2021 11:08
Last Modified:	02 Oct 2023 09:13
URI:	https://archive.lstmed.ac.uk/id/eprint/18688

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