Increased Cerebrospinal Fluid Ganglioside GD3 Concentrations as a Marker of Microglial Activation in HIV Type 1 Infection

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Abstract
Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) early in the infectious course. The predominant, productively infected cell type within the CNS is the microglial cell. We have analyzed the cerebrospinal fluid (CSF) levels of the ganglioside GD3, a microglia/macrophage and astrocyte marker, in 22 HIV-1-infected individuals at different stages of the disease, and in 44 age-matched HIV-negative, healthy controls. To distinguish between microglial/macrophage and astroglial involvement, the GD3 levels were compared with CSF levels of the glial fibrillary acidic protein (GFAp), which is expressed exclusively in astrocytes. A significantly higher mean CSF concentration of GD3 was found in HIV-1-infected patients compared to controls (56.7 and 40.1 nmol/L, respectively, p < 0.001). Seven of 22 HIV-1-infected patients had increased CSF levels of GD3 (above mean + 2 SD in controls), all but one of these had normal levels of GFAp, indicating a microglial activation or proliferation as the major source of the increased GD3 levels.