Plasmodium falciparumAntigenic Variation: Relationships between In Vivo Selection, Acquired Antibody Response, and Disease Severity

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Abstract
BackgroundVariant surface antigens (VSA) on Plasmodium falciparum–infected erythrocytes are potentially important targets of immunity to malaria. We previously identified a VSA phenotype—VSA with a high frequency of antibody recognition (VSAFoRH)—that is associated with young host age and severe malaria. We hypothesized that VSAFoRH are positively selected by host molecules such as intercellular adhesion molecule 1 (ICAM1) and CD36 and dominate in the absence of an effective immune response. Here, we assessed, in 115 Kenyan children, the potential role played by in vivo selection pressures in either favoring or selecting against VSAFoRH among parasites that cause malaria MethodsWe tested for associations between VSAFoRH and (1) the repertoire of VSA antibodies carried by children at the time of acute malaria and (2) polymorphisms in ICAM1 (K29M) and CD36 (T188G) that could potentially reduce the positive selection of VSAFoRH ResultsAn expected negative association between VSA antibody repertoire and VSAFoRH was observed in children with nonsevere malaria. However, this association did not extend to children with severe malaria, many of whom apparently had well-developed VSA antibody responses despite being infected by parasites expressing VSAFoRH. There was no evidence for involvement of CD36 or ICAM1 in positive selection of VSAFoRH. On the contrary, a weak positive association between carriage of the CD36 (T188G) allele and VSAFoRH was observed in children with severe malaria ConclusionThe association between the VSAFoRH parasite phenotype and severe malaria cannot be explained simply in terms of the total repertoire of VSA antibodies carried at the time of acute disease

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