P12.04
Background: Chronic HIV-1 infection is characterized by inflammation and also by anaemia. Erythrocyte apoptosis (erythroptosis) may contribute to anaemia and may also drive production of phagocytic monocytes/macrophages. In this study we investigated erythroptosis in asymptomatic, untreated HIV-1 infection and the relationship between erythrocyte death and phagocytic monocyte activity.
Methods: A total of 44 chronically HIV-1 infected individuals (CD4 count>200) and 33 matched uninfected individuals were included. Erythrocytes were stained with annexin V for determining ex vivo levels of erythroptosis. Erythrocytes were also subjected to oxidative stress in vitro (5mM hydrogen peroxide), in the presence or absence of the antioxidant N-acetyl cysteine (NAC). Finally, erythrocytes were also stained with CFSE and then incubated with purified autologous monocytes to monitor phagocytosis.
Results: HIV-1 infected individuals had reduced haemoglobin levels (12.9g/dL vs. 14.1g/dL, p=0.017). This was mirrored in decreased RCC. Significantly higher erythrocyte annexin V expression was observed (13.4% vs. 10.4%, p=0.0189). Annexin V expression increased in both groups when exposed to hydrogen peroxide. NAC significantly reduced the percentage of apoptotic RBCs in the control group (20±5.1% to 15±4.4%, p=0.006), but not the HIV-1 group (18.3±5.0% to 16±5.2%, p=0.065). There was a significant increase in the percentage inflammatory monocytes (CD14+CD16+) in the HIV-1 group (8.3±3.5% vs. 5.3±3.8% p=0.0054). The expanded inflammatory monocytes were more erythrophagocytic than classical monocytes, and preferentially phagocytosed apoptotic erythrocytes (phagocytic index 2.9% vs. 5.2%, p=0.008).
Conclusions: Significant reduction in haemoglobin levels in untreated chronic HIV-1 infection was associated with increased erythroptosis. Inflammatory monocytes displayed enhanced uptake of erythrocytes. Limiting inflammatory toxicities may counteract the development of anaemia and associated monocyte changes in HIV-1 infection.
