Overexpression of lymphocytic GD3 ganglioside and presence of anti-GD3 antibodies in patients with HIV infection.

Abstract

This study was undertaken to analyze the role of disialoganglioside GD3 in HIV infection and disease progression. We report here the results obtained by both ex vivo and in vitro experiments on (1) surface and cytoplasmic expression and distribution of GD3 in HIV-infected cells, (2) the presence of anti-GD3 antibodies in sera of patients with HIV infection in various stages of the disease, and (3) the association of GD3 expression with HIV-related apoptotic events. GD3 expression was determined by high-performance thin-layer chromatography (HPTLC) and lipid-bound sialic acid and by static and flow cytometric analyses in peripheral blood lymphocytes from 22 AIDS patients, 20 anti-HIV Ab(+) asymptomatic subjects, and 25 healthy donors. Results obtained clearly indicated a significantly higher expression of plasma membrane GD3 content in lymphocytes from HIV-infected patients with respect to healthy controls. These HIV-induced perturbations of glycosphingolipid metabolism could be detected in all stages of the disease, including asymptomatic individuals. In addition, a significant percentage of patients showing disease progression displayed in serum samples an increased presence of anti-GD3 antibodies. Interestingly, ex vivo studies of lymphocytes from patients with HIV infection also indicated that GD3 expression is strictly associated with annexin V binding, an early marker of apoptosis. Moreover, cytofluorimetric analysis showed that virtually all anti-p24 Ab-positive cells were also immunolabeled with anti-GD3 antibodies. Accordingly, in vitro studies showed a significant redistribution and increase in GD3 expression in cultured U937 cells chronically infected with HIV-1 with respect to uninfected counterparts. In conclusion, our data clearly indicate that a significant increase in GD3 content in HIV-infected lymphocytes can occur and that this GD3 overexpression is paralleled by the presence of anti-GD3 antibodies in the plasma of patients. This is the first demonstration that disialoganglioside GD3, independent of the therapeutic schedule employed, can be considered as one of the early markers of HIV infection and can contribute to the early events leading to T cell depletion by apoptosis.