4.7 Article

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

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BIOORGANIC & MEDICINAL CHEMISTRY
卷 18, 期 11, 页码 3747-3752

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2010.04.059

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Malaria; Antibody responses; GPI; Synthetic oligosaccharides; Microarrays

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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. (C) 2010 Elsevier Ltd. All rights reserved.

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