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.
AIDS (London, England)
University of Oxford, Nuffield Department of Medicine, Oxford, United Kingdom UiT The Arctic University of Norway University Hospital of North Norway, Tromsø, Norway Department of Clinical Research International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom Biomedical Research and Training Institute, Harare, Zimbabwe Liverpool School of Tropical Medicine, Liverpool, UK Malawi-Liverpool Wellcome Trust Clinical Research Program, Blantyre, Malawi.