PubMed · 8035256
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A Katz. 1994. AIDS dementia complex.. https://pubmed.ncbi.nlm.nih.gov/8035256/
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This study comprises the 255 adult AIDS patients treated at Ullevål hospital 1983-1995. These patients, fulfilling the Centers of Disease Control (CDC) clinical criteria for AIDS, correspond to 91% of all adult AIDS cases in Oslo. By the end of the study period, 44 patients were alive and 211 had died. Full autopsy was performed on 153 (73%) of the deceased. Supplementary analyses were carried out on the 344 patients (225 deceased) fulfilling the U.S. definition of AIDS, which includes CD4 cell counts below 200 cells/mm3. In the autopsy group, histologically verified non-Hodgkin B-cell lymphoma was found in 29 cases (19%). Nineteen of these (12%) had primary central nervous system (PCNS) lymphoma. Survival curves indicate that PCNS lymphoma constitutes a small risk early in the AIDS stage, but it has a serious impact on long-term survival. For patients not contracting other fatal diseases, one fourth are estimated to die of PCNS lymphoma within about 3 years. Comparison of clinical diagnoses and autopsy results show that PCNS lymphoma has been difficult to separate from other CNS disorders, which probably has caused marked underestimation of the incidence in previous assessments. We conclude that PCNS lymphoma is a major threat to long-term survival in AIDS victims.
HIV-1 invades the central nervous system early during viral infection, but neurologic impairment usually occurs years later. The strongest predictor for clinical dementia is the absolute numbers of immunocompetent brain macrophages. Thus, how monocytes penetrate the brain during disease remains critical for understanding the neuropathogenic mechanisms of HIV-1 encephalitis. To these ends, we constructed an artificial blood-brain barrier (BBB) consisting of a matrix-coated membrane with brain microvascular endothelial cells (BMVEC) on one side and astrocytes on the other. Astrocyte endfeet contacted the monolayer of BMVEC that formed tight junctions. To determine the role of viral and immune factors in monocyte penetration across the BBB, HIV-infected or uninfected monocytes with or without immune stimulation were placed onto the upper chamber of the BBB model system. Placement of immune-stimulated (LPS-treated) cells onto the BBB construct elicited gaps between BMVEC, with bulging of nuclear zones and increased numbers of vesicular Golgi complexes and endoplasmic reticulum. This correlated with a profound increase (up to 20-fold) in the number of migrating cells. Viral infection did not enhance monocyte migration. The activated monocytes showed increased numbers of philopodia, lysosomes, and vesicular Golgi complexes and expressed large levels of proinflammatory cytokines (TNF-alpha, IL-6, and IL-10). These data suggest that a major mechanism for the transendothelial migration of monocytes during HIV encephalitis is the immune activation that accompanies viral infection of the central nervous system.
BACKGROUND: 15-30% of patients infected with HIV will develop a debilitating dementia. Whilst HIV enters the brain soon after infection, presumably within monocyte-derived macrophages, not all patients with HIV become demented. Blood monocytes probably cross the blood-brain barrier and give rise ultimately to parenchyma macrophages. We looked for a specific monocyte subset in AIDS patients with dementia. METHODS: Peripheral blood monocytes from three groups were compared: AIDS patients with (n = 12) and without (n = 11) dementia, and ten HIV seronegative healthy controls. We used flow cytometry to analyse monocytes, and cell lysis and apoptosis assays to examine monocyte effects on human brain cells in vitro. FINDINGS: We found a unique subset of monocytes in patients with AIDS dementia. These monocytes were more dense and granular and expressed CD14/CD16 and CD14/CD69. Means (SD) for CD14/CD16 in HIV-negative controls and in AIDS non-dementia and AIDS dementia patients were 6.5% (4), 16% (13), and 37% (21), respectively (p = 0.008 between the two groups of patients). The corresponding means for CD14/CD69 were 7% (6), 8% (10), and 69% (18) (p < 0.0001). INTERPRETATION: CD69 is a member of the natural-killer-cell gene complex that is expressed after activation. Supernatants from cultures containing these dense cells can trigger apoptosis of human brain cells in vitro. The monocyte subset we found in patients with AIDS dementia might enter the brain and expose neural cells to toxic factors.