Dataset Information

Characterization of Cellular Immune Responses in Thai Individuals With and Without HIV-Associated Neurocognitive Disorders.

ABSTRACT: HIV-associated neurocognitive disorder (HAND) remains a challenge despite antiretroviral therapy (ART), and has been linked to monocyte/macrophage (M/M) migration to the brain. Due to the potential impact of T cell effector mechanisms in eliminating activated/HIV-infected M/M, T cell activation may play a role in the development of HAND. We sought to investigate the relationship between cognition and both CD8+ T cell activation (HLA-DR+/CD38+) and HIV-specific CD8+ T cell responses at the time of HIV diagnosis and 12 months postinitiation of ART. CD8+ T cell activation was increased in HAND compared to cognitive normal (NL) individuals and correlated directly with plasma viral load and inversely with the cognitive status. In addition, Gag-specific cytolytic activity (CD107a/b+) was decreased in HAND compared with NL individuals and correlated with their neurological testing, suggesting a potential role of cytotoxic CD8+ T cells in the mechanism of HAND development.

SUBMITTER: Ratto-Kim S

PROVIDER: S-EPMC6080108 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Characterization of Cellular Immune Responses in Thai Individuals With and Without HIV-Associated Neurocognitive Disorders.

Ratto-Kim Silvia S Schuetz Alexandra A Sithinamsuwan Pasiri P Barber John J Hutchings Nicholas N Lerdlum Sukalaya S Fletcher James L K JLK Phuang-Ngern Yuwadee Y Chuenarom Weerawan W Tipsuk Somporn S Pothisri Mantana M Jadwattanakul Tanate T Jirajariyavej Supunnee S Sajjaweerawan Chayada C Akapirat Siriwat S Chalermchai Thep T Suttichom Duanghathai D Kaewboon Boot B Prueksakaew Peeriya P Karnsomlap Putthachard P Clifford David D Paul Robert H RH de Souza Mark S MS Kim Jerome H JH Ananworanich Jintanat J Valcour Victor V

AIDS research and human retroviruses 20180612 8

HIV-associated neurocognitive disorder (HAND) remains a challenge despite antiretroviral therapy (ART), and has been linked to monocyte/macrophage (M/M) migration to the brain. Due to the potential impact of T cell effector mechanisms in eliminating activated/HIV-infected M/M, T cell activation may play a role in the development of HAND. We sought to investigate the relationship between cognition and both CD8+ T cell activation (HLA-DR+/CD38+) and HIV-specific CD ...[more]

PMID: 29737194

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Project description:In the USA, increased cerebrospinal fluid (CSF) inflammatory cytokines have been observed in antiretroviral therapy (ART)-naive, HIV-seropositive individuals with HIV-associated neurocognitive disorder (HAND). We characterized the relationship between HAND and CSF biomarker expression in ART-naive, HIV-seropositive individuals in Rakai, Uganda. We analyzed CSF of 78 HIV-seropositive, ART-naive Ugandan adults for 17 cytokines and 20 neurodegenerative biomarkers via Luminex multiplex assay. These adults underwent neurocognitive assessment to determine their degree of HAND. We compared biomarker concentrations between high and low CD4 groups and across HAND classifications, adjusting for multiple comparisons. Individuals with CD4 <200 cells/μL (N = 38) had elevated levels of CSF Interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, matrix metalloproteinase (MMP)-1, MMP-7, and S100 calcium-binding protein B (S100B) and lower levels of amyloid β42. Individuals with CD4 351-500 cells/μL (N = 40) had significantly higher CSF levels of interleukin (IL)-1β, amyloid β42, and soluble receptor for advanced glycation end products (sRAGE). Increasing levels of S100B, platelet-derived growth factor-AA (PDGF-AA), brain-derived neurotrophic factor (BDNF), and sRAGE were associated with decreased odds of mild neurocognitive disorder (n = 22) or HIV-associated dementia (n = 15) compared with normal function (n = 30) or asymptomatic neurocognitive impairment (n = 11). Increased levels of interferon (IFN)-γ were associated with increased odds of mild neurocognitive impairment or HIV-associated dementia relative to normal or asymptomatic neurocognitive impairment. Proinflammatory CSF cytokines, chemokines, and neurodegenerative biomarkers were present in increasing concentrations with advanced immunosuppression and may play a role in the development of HAND. The presence of select CNS biomarkers may also play a protective role in the development of HAND.

Dataset Information

Characterization of Cellular Immune Responses in Thai Individuals With and Without HIV-Associated Neurocognitive Disorders.

Publications

Characterization of Cellular Immune Responses in Thai Individuals With and Without HIV-Associated Neurocognitive Disorders.

Similar Datasets

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