Proteomic analyses of monocytes obtained from Hispanic women with HIV‐associated dementia show depressed antioxidants

Monocyte ingress into the brain during progressive human immunodeficiency virus (HIV-1) infection parallels the severity of cognitive impairments. Although activated monocyte phenotypes emerge during disease, the functional correlates of these cells remain unresolved. To this end, we studied the proteome of blood-derived monocytes obtained from Hispanic women with the most severe form of HIV-associated neurocognitive disorder, HIV-associated dementia (HAD). Monocytes isolated from peripheral blood mononuclear cells by CD14+ immunoaffinity column chromatography were >95% pure. Cells were recovered from five patients without evidence of cognitive impairment and four with HAD and analyzed by two-dimensional difference gel electrophoresis and tandem mass spectrometry. Importantly, ADP ribosylhydrolase, myeloperoxidase, thioredoxin, peroxiredoxin 3, NADPH, and GTPase activating protein were all downregulated in HAD. In regards to myeloperoxidase, thioredoxin, and peroxiredoxin 3 these changes were validated in an additional cohort of 30 patients by flow cytometry. We conclude that deficits in monocyte antioxidant proteins lead to neuronal damage through the loss of hydrogen peroxide scavenging capabilities, thus exposing neurons to apoptosis-inducing factors. Altered monocyte functions therefore may contribute to the development and progression of HAD.