%0 Journal Article
%T The cerebrospinal fluid proteome in HIV infection: change associated with disease severity
%A Thomas E Angel
%A Jon M Jacobs
%A Serena S Spudich
%A Marina A Gritsenko
%A Dietmar Fuchs
%A Teri Liegler
%A Henrik Zetterberg
%A David G Camp
%A Richard W Price
%A Richard D Smith
%J Clinical Proteomics
%D 2012
%I BioMed Central
%R 10.1186/1559-0275-9-3
%X After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral therapy and correlated abundances of identified proteins a) within and between subjects, b) with all other proteins across the entire sample set, and c) with "external" CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) ¡Ü -0.3 and ¡Ý0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node.Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.While central nervous system (CNS) HIV infection is a nearly universal facet of systemic infection, its course and clinical manifestatio
%K Amyloid
%K Cerebrospinal fluid
%K HIV
%K Pathway
%K Proteomics
%U http://www.clinicalproteomicsjournal.com/content/9/1/3