Background:  HIV-1 infection leads to progressive immune dysregulation both systemically and within the central nervous system (CNS). Together, CNS infection and immune dysregulation induce CNS injury presenting as AIDS dementia complex (ADC).

Methods:  To better define cerebrospinal fluid (CSF) and blood immunological biomarker profiles characteristic of ADC, we examined an array of cytokines using a bead immunoassay technique that measures multiple analytes in a small volume. Cross-sectional survey of cytokine changes in archived CSF and blood samples of 150 untreated subjects from 3 clinical centers segregated by HIV status (including 20 HIV^– and 14 with primary HIV infection), CD4 count (neuroasymptomatic  subjects:  20 with CD4 >350 cells/mL; 18 with 200 to 249; 13 with 50 to 199, and 21 with <50) and ADC (12 stage 0.5 and 31 stage 2 to 4). We used Luminex Instrumentation and multiplex reagents from LINCO to measure 29 analytes in CSF and blood:  interleukin (IL) -1α, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p40), IL-12 (p70), IL-13, IL-15, IL-17, sCD40L, epidermal growth factor (EGF), eotaxin, fractalkine, granulocyte colony stimulating factor (GCSF), granulocyte/macrophage colony stimulating factor (GMCSF), interferon (IFN)-γ, interferon-inducible protein (IP) -10, monocyte chemotactic protein (MCP) -1, macrophage inhibitory factor (MIP) -1α, MIP-1β, tumor growth factor (TGF) -α, tumor necrosis factor (TNF) -α, and vascular endothelial growth factor (VEGF). Range of quantitation: 3.2-10,000 pg/mL for each.

Results:  CSF had lower concentrations of analytes than blood with exceptions of MCP-1 and IP-10. Several patterns of cytokine changes were observed in both fluids, including elevations in CSF levels across all HIV⁺ groups compared to HIV^– (eg, IP-10, IL-1α) and elevations in ADC compared to neuroasymptomatic HIV⁺ subjects (MCP-1, IL-1ra). Blood patterns also varied. They included elevations across HIV⁺ groups compared to HIV^– (IP-10), but more commonly showed decreases in cytokines in HIV⁺ compared to HIV^–, either across all HIV⁺ groups, or progressing with fall in CD4 counts (fractalkine, IL-13, IL-17, and VEGF). Disproportionate elevations (eotaxin, MCP-1, VEGF) or decreases (IL-17, IFN-γ, IL-12(p40)) were also noted in ADC stage 2 to 4 compared to neuroasymptomatic HIV⁺ subjects. (Above differences were significant by ANOVA with post hoc, p <0.05 to <0.001).

Conclusions:  Multiplex bead technology affords an economical method of analyzing CSF and blood cytokines and other biomarkers. Our results extend previous findings using single cytokine assays, identify new potential CSF markers, and suggest that a combination biomarker panel can be the basis of objective laboratory-based ADC diagnosis as well as provide insights into neuropathogenesis.