Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study

作者：Magnus Gisslén, Richard W. Price, Ulf Andréasson, Niklas Norgren, Staffan Nilsson, Lars Hagberg, Dietmar Fuchs, Serena Spudich, Kaj Blennow, Henrik Zetterberg · 发表于：EBioMedicine · 年份：2015 · DOI：10.1016/j.ebiom.2015.11.036 · 被引用次数：500 · 研究领域：HIV Research and Treatment、Prion Diseases and Protein Misfolding、Multiple Sclerosis Research Studies

BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. METHODS: To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. FINDINGS: Plasma and CSF NFL concentrations were very highly correlated (r = 0.89, P < 0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-n...