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

• Published in: Bioorganic & medicinal chemistry 2010-06, Vol.18 (11), p.3747-3752
• Main Authors: Tamborrini, Marco, Liu, Xinyu, Mugasa, Joseph Paschal, Kwon, Yong-Uk, Kamena, Faustin, Seeberger, Peter H., Pluschke, Gerd
• Format: Article
• Language: English
• Subjects: Age Factors; Antibodies - analysis; Antibodies - immunology; Antibody responses; Biological and medical sciences; Child, Preschool; Epitope Mapping; Epitopes - analysis; Glucosamine - analysis; Glycosylphosphatidylinositols - immunology; GPI; Human protozoal diseases; Humans; Immunity, Humoral; Infant; Infectious diseases; Inositol - analysis; Investigative techniques, diagnostic techniques (general aspects); Malaria; Malaria - immunology; Mannose - analysis; Medical sciences; Microarrays; Miscellaneous. Technology; Parasitic diseases; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polysaccharides - analysis; Protozoal diseases; Severity of Illness Index; Synthetic oligosaccharides
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.04.059

A carbohydrate microarray spotted with synthetic GPI-glycans provides insights into the anti-malarial antibody response in healthy and malaria diseased individuals. 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 Man 3-GPI and Man 4-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.