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From the Department of Neurology (Dr. Luo), First China Hospital Medical University, Shenyang, P.R. China; Laboratory of Neuroregeneration, Center for Neurovirology and Neurodegenerative Disorders (Drs. Carlson and Gendelman, and T.M. Biskup) and the Departments of Pathology and Microbiology (Drs. Carlson and Gendelman, and T.M. Biskup), Preventative and Societal Medicine (Drs. Stoner and Anderson), and Internal Medicine (Dr. Gendelman), University of Nebraska Medical Center, Omaha; and the Departments of Microbiology and Physical Medicine and Specialized NeuroSciences Research Program (Drs. Wojna, Mayo, and Meléndez), University of Puerto Rico Medical Sciences Campus, San Juan.
Address correspondence and reprint requests to Dr. Howard E. Gendelman, Center for Neurovirology and Neurodegenerative Disorders, 985215 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5215; e-mail: hegendel{at}unmc.edu
Background: Specific proteins produced from monocytes may be linked to the pathogenesis and aid in the diagnosis of HIV-1–associated dementia (HAD).
Objective: The authors assessed whether a diagnostic phenomic protein profile could be obtained from monocyte-derived macrophages (MDM) from HIV-1–infected patients with cognitive impairment.
Methods: Twenty-one HIV-1–infected Hispanic women and 10 seronegative controls matched by age and sex were followed at the University of Puerto Rico Medical Sciences Campus, where neuropsychological, immune, and viral parameters were tested. Monocytes were recovered by Percoll gradient centrifugation from peripheral blood mononuclear cells. MDM lysates were prepared after 7 days of cultivation and protein profiles analyzed by surface enhanced laser desorption/ionization (SELDI)–time of flight (TOF) ProteinChip tests. Classification trees were prepared for statistical analyses.
Results: A total of 177 protein peaks from 2 to 80 kDa were evaluated in 31 patient MDM lysates by SELDI-TOF ProteinChip assays. Select protein peaks, at 5028 and 4320 Da, separated HIV-1–infected from HIV-1–seronegative subjects with a sensitivity of 100% and a specificity of 80%. Thirty-eight peaks were used to differentiate HIV-1–infected subjects with and without cognitive impairment. A 4348 Da protein separated the two groups with a sensitivity of 100% and a specificity of 75%.
Conclusions: The identification of unique phenomic MDM profiles from cognitively impaired HIV-1–infected patients supports the hypothesis that changes in monocyte function parallel the development of HAD.
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