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

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 exp ression and distribution of GD3 in HIV-infected cells, (2) the presence of anti-GD3 antibodies in sera of patients with HIV infection in various stage s of the disease, and (3) the association of GD3 expression with HIV-relate d 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 patie nts, 20 anti-HIV Ab(+) asymptomatic subjects, and 25 healthy donors. Result s obtained clearly indicated a significantly higher expression of plasma me mbrane GD3 content in lymphocytes from HIV-infected patients with respect t o healthy controls. These HIV-induced perturbations of glycosphingolipid me tabolism could be detected in all stages of the disease, including asymptom atic individuals. In addition, a significant percentage of patients showing disease progression displayed in serum samples an increased presence of an ti-GD3 antibodies. Interestingly, ex vivo studies of lymphocytes from patie nts with HIV infection also indicated that GD3 expression is strictly assoc iated with annexin V binding, an early marker of apoptosis. Moreover, cytof luorimetric analysis showed that virtually all anti-p24 Ab-positive cells w ere also immunolabeled with anti-GD3 antibodies. Accordingly, in vitro stud ies showed a significant redistribution and increase in GD3 expression in c ultured U937 cells chronically infected with HIV-1 with respect to uninfect ed counterparts. In conclusion, our data clearly indicate that a significan t increase in GD3 content in HIV-infected lymphocytes can occur and that th is GD3 overexpression is paralleled by the presence of anti-GD3 antibodies in the plasma of patients. This is the first demonstration that disialogang lioside GD3, independent of the therapeutic schedule employed, can be consi dered as one of the early markers of HIV infection and can contribute to th e early events leading to T cell depletion by apoptosis.