title: OTK18 levels in plasma and cerebrospinal fluid correlate with viral load and CD8 T-cells in normal and AIDS patients.
abstract: OTK18 is a C2H2 type zinc finger protein expressed by human macrophages following HIV infection. OTK18 possesses antiretroviral activity, and its processing products accumulate in the cytoplasm of perivascular brain macrophages in advanced HIV encephalitis cases. Since the regulation of OTK18 expression in living patients following human immunodeficiency virus-1 (HIV-1) infection is unknown, our objective is to investigate the first cohort study on OTK18 protein levels in living patients. We assessed OTK18 levels in plasma and cerebrospinal fluid (CSF) in 44 living patients with or without HIV-1 infection, with diverse demographic and clinical background. A novel high-sensitivity OTK18 ELISA system was developed to measure OTK18 levels in CSF and plasma using custom made biotinylated monoclonal antibodies against OTK18. The correlation of OTK18 levels with epidemiological parameters was statistically analyzed. Multiple linear regression modeling suggested that plasma OTK18 levels for HIV-1-positive subjects were only about one sixth of that for HIV-1-negative subjects. Higher CD8 T-cell counts were associated with higher levels of OTK18. Using proportional odds logistic regression, we showed that HIV-1-positive patients have significantly lower OTK18 in CSF samples, but we did not observe significant correlation between CD8 T-cell counts and CSF OTK18 levels. OTK18 levels in both plasma and CSF are significantly lower in HIV-1-positive subjects as compared to HIV-1-negative subjects. Plasma OTK18 levels are positively correlated to CD8 T-cell counts, independent of HIV-1 status.
authors.affiliation: Center for Neurovirology and Neurodegenerative Disorders and the Department of Pharmacology and Experimental Neuroscience, 985880 University of Nebraska Medical Center, Omaha, NE 68918-5880, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Buescher
authors.forename: Fenghai
authors.initials: F
authors.lastname: Duan
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.forename: Tsuneya
authors.initials: T
authors.lastname: Ikezu
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism*; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D014157:Transcription Factors / Q000032:analysis*; D019562:Viral Load
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C104178:ZNF175 protein, human
references.citation: J Biomol Screen. 1999;4(2):67-73
references.pmid: 10838414
references.citation: Immunology. 1995 Jul;85(3):475-84
references.pmid: 7558138
references.citation: BMC Infect Dis. 2005 Nov 02;5:98
references.pmid: 16266436
references.citation: J Immunol. 2004 Jan 1;172(1):381-91
references.pmid: 14688346
references.citation: Ann Neurol. 1986 Jun;19(6):517-24
references.pmid: 3729308
references.citation: Proteomics. 2005 Aug;5(13):3506-19
references.pmid: 16104058
references.citation: J Infect Dis. 2005 Mar 15;191(6):890-8
references.pmid: 15717264
references.citation: Proteomics. 2005 Aug;5(13):3226-45
references.pmid: 16104056
references.citation: J Neuroimmunol. 2004 May;150(1-2):186-98
references.pmid: 15081264
references.citation: AIDS. 1997;11 Suppl A:S35-45
references.pmid: 9451964
references.citation: Genomics. 1996 Feb 1;31(3):376-9
references.pmid: 8838321
references.citation: Stem Cells. 2000;18(4):230-44
references.pmid: 10924089
references.citation: J Neurovirol. 2004;10 Suppl 1:44-51
references.pmid: 14982739