Glycosylphosphatidylinositol anchors of Plasmodium falciparum: Molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis

Induction of proinflammatory cytokine responses by glycosylphosphatidylinos itols (GPIs) of intraerythrocytic Plasmodium falciparum is believed to cont ribute to malaria pathogenesis. In this study, we purified the GPIs of P. f alciparum to homogeneity and determined their structures by biochemical deg radations and mass spectrometry. The parasite GPIs differ from those of the host in that they contain palmitic (major) and myristic (minor) acids at C -2 of inositol, predominantly C18:0 and C18:1 at sn-1 and sn-2, respectivel y, and do not contain additional phosphoethanolamine substitution in their core glycan structures. The purified parasite GPIs can induce tumor necrosi s factor a release from macrophages. We also report a new finding that adul ts who have resistance to clinical malaria contain high levels of persisten t anti-GPI antibodies, whereas susceptible children lack or have low levels of short-lived antibody response. Individuals who were not exposed to the malaria parasite completely lack anti-GPI antibodies. Absence of a persiste nt anti-GPI antibody response correlated with malaria-specific anemia and f ever, suggesting that anti-GPI antibodies provide protection against clinic al malaria. The antibodies are mainly directed against the acylated phospho inositol portion of GPIs. These results are likely to be valuable in studie s aimed at the evaluation of chemically defined structures for toxicity ver sus immunogenicity with implications for the development of GPI-based thera pies or vaccines.