PMID- 27995575 OWN - NLM STAT- MEDLINE DCOM- 20180301 LR - 20210109 IS - 1538-2443 (Electronic) IS - 1355-0284 (Print) IS - 1355-0284 (Linking) VI - 23 IP - 3 DP - 2017 Jun TI - Cerebrospinal fluid biomarkers and HIV-associated neurocognitive disorders in HIV-infected individuals in Rakai, Uganda. PG - 369-375 LID - 10.1007/s13365-016-0505-9 [doi] AB - In the USA, increased cerebrospinal fluid (CSF) inflammatory cytokines have been observed in antiretroviral therapy (ART)-naive, HIV-seropositive individuals with HIV-associated neurocognitive disorder (HAND). We characterized the relationship between HAND and CSF biomarker expression in ART-naive, HIV-seropositive individuals in Rakai, Uganda. We analyzed CSF of 78 HIV-seropositive, ART-naive Ugandan adults for 17 cytokines and 20 neurodegenerative biomarkers via Luminex multiplex assay. These adults underwent neurocognitive assessment to determine their degree of HAND. We compared biomarker concentrations between high and low CD4 groups and across HAND classifications, adjusting for multiple comparisons. Individuals with CD4 <200 cells/muL (N = 38) had elevated levels of CSF Interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-alpha, matrix metalloproteinase (MMP)-1, MMP-7, and S100 calcium-binding protein B (S100B) and lower levels of amyloid beta42. Individuals with CD4 351-500 cells/muL (N = 40) had significantly higher CSF levels of interleukin (IL)-1beta, amyloid beta42, and soluble receptor for advanced glycation end products (sRAGE). Increasing levels of S100B, platelet-derived growth factor-AA (PDGF-AA), brain-derived neurotrophic factor (BDNF), and sRAGE were associated with decreased odds of mild neurocognitive disorder (n = 22) or HIV-associated dementia (n = 15) compared with normal function (n = 30) or asymptomatic neurocognitive impairment (n = 11). Increased levels of interferon (IFN)-gamma were associated with increased odds of mild neurocognitive impairment or HIV-associated dementia relative to normal or asymptomatic neurocognitive impairment. Proinflammatory CSF cytokines, chemokines, and neurodegenerative biomarkers were present in increasing concentrations with advanced immunosuppression and may play a role in the development of HAND. The presence of select CNS biomarkers may also play a protective role in the development of HAND. FAU - Abassi, Mahsa AU - Abassi M AD - University of Minnesota, Minneapolis, MN. AD - Infectious Diseases Institute, Kampala, Uganda. FAU - Morawski, Bozena M AU - Morawski BM AD - University of Minnesota, Minneapolis, MN. AD - Infectious Diseases Institute, Kampala, Uganda. FAU - Nakigozi, Gertrude AU - Nakigozi G AD - Rakai Health Sciences Program, Entebbe, Uganda. FAU - Nakasujja, Noeline AU - Nakasujja N AD - Infectious Diseases Institute, Kampala, Uganda. AD - Makerere University, Kampala, Uganda. FAU - Kong, Xiangrong AU - Kong X AD - Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. FAU - Meya, David B AU - Meya DB AD - University of Minnesota, Minneapolis, MN. AD - Infectious Diseases Institute, Kampala, Uganda. AD - Makerere University, Kampala, Uganda. FAU - Robertson, Kevin AU - Robertson K AD - University of North Carolina, Chapel Hill, NC. FAU - Gray, Ronald AU - Gray R AD - Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. FAU - Wawer, Maria J AU - Wawer MJ AD - Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. FAU - Sacktor, Ned AU - Sacktor N AD - Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Boulware, David R AU - Boulware DR AD - University of Minnesota, Minneapolis, MN. LA - eng GR - U01 AI089244/AI/NIAID NIH HHS/United States GR - R01 NS086312/NS/NINDS NIH HHS/United States GR - R01 AI110324/AI/NIAID NIH HHS/United States GR - T32 AI055433/AI/NIAID NIH HHS/United States GR - MR/M007413/1/MRC_/Medical Research Council/United Kingdom GR - R01 MH099733/MH/NIMH NIH HHS/United States GR - R25 TW009345/TW/FIC NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20161219 PL - United States TA - J Neurovirol JT - Journal of neurovirology JID - 9508123 RN - 0 (Amyloid beta-Peptides) RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Interleukin-2) RN - 0 (Peptide Fragments) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (S100 Calcium Binding Protein beta Subunit) RN - 0 (S100B protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (amyloid beta-protein (1-42)) RN - 0 (platelet-derived growth factor A) RN - 0 (sRAGE protein, human) RN - 187348-17-0 (Interleukin-12) RN - 7171WSG8A2 (BDNF protein, human) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 3.4.24.23 (MMP7 protein, human) RN - EC 3.4.24.23 (Matrix Metalloproteinase 7) RN - EC 3.4.24.7 (MMP1 protein, human) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM CIN - J Neurovirol. 2019 Dec;25(6):899-900. PMID: 31278533 CIN - J Neurovirol. 2019 Dec;25(6):897-898. PMID: 31278534 MH - AIDS Dementia Complex/*cerebrospinal fluid/*diagnosis/immunology/physiopathology MH - Adult MH - Amyloid beta-Peptides/cerebrospinal fluid/immunology MH - Biomarkers/cerebrospinal fluid MH - Brain-Derived Neurotrophic Factor/cerebrospinal fluid/immunology MH - CD4 Lymphocyte Count MH - CD4-Positive T-Lymphocytes/*immunology/pathology MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/cerebrospinal fluid/immunology MH - Humans MH - Interleukin-12/cerebrospinal fluid/immunology MH - Interleukin-2/cerebrospinal fluid/immunology MH - Male MH - Matrix Metalloproteinase 1/cerebrospinal fluid/immunology MH - Matrix Metalloproteinase 7/cerebrospinal fluid/immunology MH - Middle Aged MH - Neuropsychological Tests MH - Peptide Fragments/cerebrospinal fluid/immunology MH - Platelet-Derived Growth Factor/cerebrospinal fluid/immunology MH - Prospective Studies MH - Receptor for Advanced Glycation End Products/blood/immunology MH - S100 Calcium Binding Protein beta Subunit/cerebrospinal fluid/immunology MH - Tumor Necrosis Factor-alpha/cerebrospinal fluid/immunology MH - Uganda PMC - PMC5441942 MID - NIHMS837884 OTO - NOTNLM OT - Cytokine expression OT - Dementia OT - HIV-associated neurocognitive disorders OT - Inflammation OT - Neurodegenerative biomarkers EDAT- 2016/12/21 06:00 MHDA- 2018/03/02 06:00 PMCR- 2018/06/01 CRDT- 2016/12/21 06:00 PHST- 2016/10/03 00:00 [received] PHST- 2016/12/01 00:00 [accepted] PHST- 2016/11/21 00:00 [revised] PHST- 2016/12/21 06:00 [pubmed] PHST- 2018/03/02 06:00 [medline] PHST- 2016/12/21 06:00 [entrez] PHST- 2018/06/01 00:00 [pmc-release] AID - 10.1007/s13365-016-0505-9 [doi] PST - ppublish SO - J Neurovirol. 2017 Jun;23(3):369-375. doi: 10.1007/s13365-016-0505-9. Epub 2016 Dec 19.