Cell-free mitochondrial DNA in CSF is associated with early viral rebound, inflammation, and severity of neurocognitive deficits in HIV infection

Autor: Davey M. Smith, Scott Letendre, Marta Massanella, Michelli F. Oliveira, Miguel Ramirez-Gaona, Rachel D. Schrier, Josué Pérez-Santiago, Sanjay Mehta, Susanna R. Var, Ronald J. Ellis, Sara Gianella, Mariana Cherner, Jesse D. Suben, Ben Murrell, Tyler R C Day
Rok vydání: 2015
Předmět:
Male
CD/cerebrospinal fluid/genetics/immunology Antigens
0301 basic medicine
Pediatric AIDS
Lipopolysaccharide Receptors
Gene Expression
HIV Infections
Neuropsychological Tests
Severity of Illness Index
Executive Function
chemistry.chemical_compound
0302 clinical medicine
Cerebrospinal fluid
CSF pleocytosis
Neurofilament Proteins
Receptors
Blood plasma
2.1 Biological and endogenous factors
Aetiology
Chemokine CCL2
Pediatric
Myelomonocytic/cerebrospinal fluid/genetics/immunology Chemokine CCL2/cerebrospinal fluid/genetics/immunology Chemokine CXCL10/cerebrospinal fluid/genetics/immunology Cognitive Dysfunction/*cerebrospinal fluid/complications/immunology/pathology Cross-Sectional Studies DNA
Neopterin
Middle Aged
Mitochondrial DNA
Mitochondrial
CD
Infectious Diseases
Droplet digital PCR
Neurology
Medical Microbiology
Differentiation
Mitochondrial/*cerebrospinal fluid Executive Function Female Gene Expression HIV Infections/*cerebrospinal fluid/complications/immunology/pathology HIV-1/physiology Humans Interleukin-6/cerebrospinal fluid/genetics/immunology Learning Lipopolysaccharide Receptors/cerebrospinal fluid/genetics/immunology Male Memory Middle Aged Neopterin/cerebrospinal fluid/immunology Neurofilament Proteins/cerebrospinal fluid/genetics/immunology Neuropsychological Tests Receptors
Cell Surface
HIV/AIDS
Female
Pleocytosis
medicine.symptom
Infection
Adult
Clinical Sciences
Antigens
Differentiation
Myelomonocytic
Receptors
Cell Surface
Inflammation
HAND
DNA
Mitochondrial
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Antigens
CD
Memory
Clinical Research
Virology
Genetics
medicine
Humans
Learning
Cognitive Dysfunction
Antigens
Adult Antigens
Tumor Necrosis Factor-alpha
Interleukin-6
business.industry
Inflammatory and immune system
Neurosciences
DNA
Myelomonocytic
Chemokine CXCL10
Cell Surface/genetics/immunology Severity of Illness Index Tumor Necrosis Factor-alpha/cerebrospinal fluid/genetics/immunology Droplet digital PCR Hand Inflammation Mitochondrial DNA Pleocytosis
Cross-Sectional Studies
030104 developmental biology
chemistry
Immunology
HIV-1
Neurology (clinical)
business
CD163
030217 neurology & neurosurgery
CD8
Zdroj: Journal of neurovirology, vol 22, iss 2
Pérez-Santiago, J; Schrier, RD; de Oliveira, MF; Gianella, S; Var, SR; Day, TRC; et al.(2015). Cell-free mitochondrial DNA in CSF is associated with early viral rebound, inflammation, and severity of neurocognitive deficits in HIV infection. Journal of NeuroVirology. doi: 10.1007/s13365-015-0384-5. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/7kh5q1kq
ISSN: 1538-2443
1355-0284
Popis: © 2015 Journal of NeuroVirology, Inc. Cell-free mitochondiral DNA (mtDNA) is an immunogenic molecule associated with many inflammatory conditions. We evaluated the relationship between cell-free mtDNA in cerebrospinal fluid (CSF) and neurocognitive performance and inflammation during HIV infection. In a cross-sectional analysis, we evaluated the association of mtDNA levels with clinical assessments, inflammatory markers, and neurocognitive performance in 28 HIV-infected individuals. In CSF, we measured mtDNA levels by droplet digital PCR, and soluble CD14 and CD163, neurofilament light, and neopterin by ELISA. In blood and CSF, we measured soluble IP-10, MCP-1, TNF-α, and IL-6 by ELISA, and intracellular expression of IL-2, IFN-γ, and TNF-α in CD4+ and CD8+ T cells by flow cytometry. We also evaluated the relationship between CSF pleocytosis and mtDNA longitudinally in another set of five individuals participating in an antiretroviral treatment (ART) interruption study. Cell-free CSF mtDNA levels strongly correlated with neurocognitive performance among individuals with neurocognitive impairment (NCI) (r = 0.77, p = 0.001). CSF mtDNA also correlated with levels of IP-10 in CSF (r = 0.70, p = 0.007) and MCP-1 in blood plasma (r = 0.66, p = 0.01) in individuals with NCI. There were no significant associations between inflammatory markers and mtDNA in subjects without NCI, and levels of mtDNA did not differ between subjects with and without NCI. MtDNA levels preceded pleocytosis and HIV RNA following ART interruption. Cell-free mtDNA in CSF was strongly associated with the severity of neurocognitive dysfunction and inflammation only in individuals with NCI. Our findings suggest that within a subset of subjects cell-free CSF mtDNA is associated with inflammation and degree of NCI.
Databáze: OpenAIRE
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