Bibliographic Details
| Title: |
Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection. |
| Authors: |
Hu, Zicheng1 (AUTHOR), Cinque, Paola2,3 (AUTHOR), Dravid, Ameet4,5,6 (AUTHOR), Hagberg, Lars7,8 (AUTHOR), Yilmaz, Aylin7,8 (AUTHOR), Zetterberg, Henrik9,10,11,12,13,14 (AUTHOR), Fuchs, Dietmar15 (AUTHOR), Gostner, Johanna15 (AUTHOR), Blennow, Kaj9,10 (AUTHOR), Spudich, Serena S.16 (AUTHOR), Kincer, Laura17,18 (AUTHOR), Zhou, Shuntai17,18 (AUTHOR), Joseph, Sarah Beth17,18,19 (AUTHOR), Swanstrom, Ronald18,20,21 (AUTHOR), Price, Richard W.22 (AUTHOR) richard.price@ucsf.edu, Gisslén, Magnus7,8,23 (AUTHOR) |
| Source: |
PLoS Pathogens. 9/24/2024, Vol. 20 Issue 9, p1-39. 39p. |
| Subject Terms: |
*CENTRAL nervous system injuries, *CEREBROSPINAL fluid, *ANTIRETROVIRAL agents, *HIV, *CEREBROSPINAL fluid examination, *CYTOPLASMIC filaments |
| Abstract: |
Using the Olink Explore 1536 platform, we measured 1,463 unique proteins in 303 cerebrospinal fluid (CSF) specimens from four clinical centers contributed by uninfected controls and 12 groups of people living with HIV-1 infection representing the spectrum of progressive untreated and treated chronic infection. We present three initial analyses of these measurements: an overview of the CSF protein features of the sample; correlations of the CSF proteins with CSF HIV-1 RNA and neurofilament light chain protein (NfL) concentrations; and comparison of CSF proteins in HIV-associated dementia (HAD) and neurosymptomatic CSF escape (NSE). These reveal a complex but coherent picture of CSF protein changes with highest concentrations of many proteins during CNS injury in the HAD and NSE groups and variable protein changes across the course of systemic HIV-1 progression that included two common patterns, designated as lymphoid and myeloid patterns, related to principal involvement of their underlying inflammatory cell lineages. Antiretroviral therapy reduced CSF protein perturbations, though not always to control levels. The dataset of these CSF protein measurements, along with background clinical information, is posted online. Extended studies of this unique dataset will supplement this report to provide more detailed characterization of the dynamic impact of HIV-1 infection on the CSF proteome across the spectrum of HIV-1 infection, advancing the mechanistic understanding of HIV-1-related CNS pathobiology. Author summary: We measured more than 1,400 proteins in 303 cerebrospinal fluid (CSF) specimens from a representative broad range of untreated and treated people living with HIV-1 infection (PLWH) along with uninfected controls who volunteered for our studies. The results defined a complex, but generally coherent set of changes in many immune-inflammatory proteins and several central nervous system injury biomarkers as systemic HIV-1 infection progressed. There was a marked increase in many of these protein biomarkers in individuals with HIV-associated dementia and neurosymptomatic CSF viral escape, two conditions distinguished by overt, and characteristically severe, neurological impairment. The resultant data and initial analyses advance the characterization and understanding of the evolution of HIV-driven neuropathogenesis. The large dataset from this study is posted online and available to other investigators for further analyses, extending the utility of these data and potentially aiding in developing future prevention, diagnosis and mitigation of the deleterious impact of HIV-1 infection on the brain. [ABSTRACT FROM AUTHOR] |
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