Synthetic glycosylphosphatidylinositol microarray reveals differential antibody levels and fine specificities in children with mild and severe malaria

Glycosylphosphatidylinositol (GPI) glycolipids abound on the cell surface at the merozoite stage of Plasmodium falciparum life cycle are a central toxin in malaria. The contribution of GPI specific humoral immune responses to protection against malaria pathology is not clear, since studies on the correlation between anti-GPI antibody titers and disease severity have yielded contradictory results. Here, we present the application of a carbohydrate microarray based on synthetic PfGPI glycans to assess levels and fine specificities of anti-GPI antibody responses in healthy and malaria diseased individuals. Furthermore, the age dependent development of humoral immune responses against GPI in malaria-exposed children was investigated. Anti-GPI antibodies were only rarely found in children under the age of 18 months. Sera from subjects with severe malaria and healthy children contained antibodies that recognized predominantly synthetic Man₃-GPI and Man₄-GPIs. In contrast, antibodies in sera of children with mild malaria also showed substantial reactivity with truncated glycans comprising glucosamine–inositol moieties without mannose or with only one or two mannose residues.