Modifications in acute phase and complement systems predict shifts in cognitive status of HIV-infected patients.

TitleModifications in acute phase and complement systems predict shifts in cognitive status of HIV-infected patients.
Publication TypeJournal Article
Year of Publication2017
AuthorsUbaida-Mohien, C, Lamberty, B, Dickens, AM, Mielke, MM, Marcotte, TD, Sacktor, N, Grant, I, Letendre, S, Franklin, D, Cibrowski, P, Tharakan, R, McArthur, JC, Fox, HS, Haughey, NJ
JournalAIDS
Volume31
Issue10
Pagination1365-1378
Date Published2017 06 19
ISSN1473-5571
KeywordsAcute-Phase Reaction, Adult, AIDS Dementia Complex, Cerebrospinal Fluid, CHARTER, Complement System Proteins, Computational Biology, Female, HIV Infections, Humans, Internal, Longitudinal Studies, Male, Prognosis, Proteome
Abstract

BACKGROUND: The prevalence of HIV-associated neurocognitive disorders (HAND) has not changed considerably in the last two decades. Potent antiretroviral therapy has shifted the severity of HAND to milder phenotypes, but excess morbidity and mortality continue to be associated with HAND. Changes in numerous markers of immune function, inflammation, and cellular stress have been repeatedly associated with HAND, but the underlying systems that drive these changes have not been identified.METHOD: In this study, we used systems informatics to interrogate the cerebrospinal fluid proteomic content of longitudinal samples obtained from HIV-infected adults with stably unimpaired, stably impaired, worsening, or improving neurocognitive performance.RESULTS AND CONCLUSION: The patterns of change in cerebrospinal fluid protein content implicated the induction of acute phase and complement systems as important regulators of neurocognitive status. Worsening neurocognitive performance was preceded by induction of acute phase and complement systems, whereas improving neurocognitive performance was preceded by a downregulation of these systems.

DOI10.1097/QAD.0000000000001503
Alternate JournalAIDS
PubMed ID28574961
PubMed Central IDPMC5501712
Grant ListP30 MH075673 / MH / NIMH NIH HHS / United States
R21 AG034849 / AG / NIA NIH HHS / United States
R03 MH103985 / MH / NIMH NIH HHS / United States
U54 GM115458 / GM / NIGMS NIH HHS / United States
HHSN271201000036C / MH / NIMH NIH HHS / United States
P30 GM106397 / GM / NIGMS NIH HHS / United States
R01 MH077542 / MH / NIMH NIH HHS / United States
R01 MH110246 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
R01 AA017408 / AA / NIAAA NIH HHS / United States
R01 MH096636 / MH / NIMH NIH HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
P01 MH105280 / MH / NIMH NIH HHS / United States
R01 MH071150 / MH / NIMH NIH HHS / United States