Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection.

Autor: Hu Z; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, United States of America., Cinque P; Unit of Neurovirology, San Raffaele Hospital, Milan, Italy.; Unit of Infectious Diseases, San Raffaele Hospital, Milan, Italy., Dravid A; HIV Medicine and Infectious Diseases, Poona Hospital and Research Centre, Pune, India.; Noble Hospital and Research Centre, Pune, India.; Ruby Hall Clinic, Pune, India., Hagberg L; Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden., Yilmaz A; Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden., Zetterberg H; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom.; UK Dementia Research Institute at UCL, London, United Kingdom.; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America., Fuchs D; Institute of Medical Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria., Gostner J; Institute of Medical Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria., Blennow K; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Spudich SS; Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, United States of America., Kincer L; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America., Zhou S; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America., Joseph SB; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.; UNC HIV Cure Center, University of North Carolina, Chapel Hill, North Carolina, United States of America., Swanstrom R; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.; UNC Center for AIDS Research, University of North Carolina, Chapel Hill, North Carolina, United States of America.; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina, United States of America., Price RW; Department of Neurology, University of California San Francisco, San Francisco, California, United States of America., Gisslén M; Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden.; Public Health Agency of Sweden, Solna, Sweden.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Sep 24; Vol. 20 (9), pp. e1012470. Date of Electronic Publication: 2024 Sep 24 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012470
Abstrakt: 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.
Competing Interests: HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). These organizations and companies had no role in the study design, data collection, decision to publish, or publication of the manuscript. MG has received research grants from Gilead Sciences and honoraria as speaker, DSMB committee member and/or scientific advisor from Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV, Janssen-Cilag, MSD, Novocure, Novo Nordic, Pfizer and Sanofi. These organizations and companies had no role in the study design, data collection, decision to publish, or publication of the manuscript.
(Copyright: © 2024 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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