Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV

• Published in: Scientific reports Vol. 9; no. 1; p. 8004
• Main Authors: Blokhuis, C., Peeters, C. F. W., Cohen, S., Scherpbier, H. J., Kuijpers, T. W., Reiss, P., Kootstra, N. A., Teunissen, C. E., Pajkrt, D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29-05-2019; Nature Publishing Group
• Subjects: 13/21; 631/250/255/1901; 692/308/3187; 692/617; Adolescent; Antiretroviral drugs; Biomarkers; Biomarkers - blood; Blood flow; Brain Injuries - complications; Brain Injuries - immunology; Brain Injuries - pathology; Brain Injuries - virology; C-reactive protein; CD14 antigen; Cerebrospinal fluid; Cerebrum; Chemokine CCL2 - genetics; Chemokine CXCL10 - genetics; Child; Children; Coagulation; Cognitive ability; Cognitive Dysfunction - complications; Cognitive Dysfunction - immunology; Cognitive Dysfunction - pathology; Cognitive Dysfunction - virology; Female; HIV; HIV - pathogenicity; HIV Infections - complications; HIV Infections - immunology; HIV Infections - pathology; HIV Infections - virology; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Immune response; Immunity, Cellular - genetics; Immunological memory; Inflammation - complications; Inflammation - immunology; Inflammation - pathology; Inflammation - virology; Intelligence; Interleukin 6; Male; Medical imaging; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; multidisciplinary; Neuroimaging; Pediatrics; Plasma levels; Proteins; Science; Science (multidisciplinary); Sexually transmitted diseases; Short term memory; Socioeconomics; STD; Substantia alba; White Matter - immunology; White Matter - pathology; White Matter - virology; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-44198-z

Despite treatment, immune activation is thought to contribute to cerebral injury in children perinatally infected with human immunodeficiency virus (HIV). We aimed to characterize immune activation in relation to neuroimaging and cognitive outcomes. We therefore measured immunological, coagulation, and neuronal biomarkers in plasma and cerebrospinal fluid (CSF) samples of 34 perinatally HIV-infected children aged 8–18 years, and in plasma samples of 37 controls of comparable age, sex, ethnicity, and socio-economic status. We then compared plasma biomarker levels between groups, and explored associations between plasma/CSF biomarkers and neuroimaging and cognitive outcomes using network analysis. HIV-infected children showed higher plasma levels of C-reactive protein, interferon-gamma, interferon-gamma-inducible protein-10, and monocyte chemoattractant protein-1 than controls. In HIV-infected participants, plasma soluble CD14 was positively associated with microstructural white matter (WM) damage, and plasma D-dimer was negatively associated with WM blood flow. In CSF, IL-6 was negatively associated with WM volume, and neurofilament heavy-chain (NFH) was negatively associated with intelligence quotient and working memory. These markers of ongoing inflammation, immune activation, coagulation, and neuronal damage could be used to further evaluate the pathophysiology and clinical course of cerebral and cognitive deficits in perinatally acquired HIV.