Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria

Abstract

BackgroundPlasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria.MethodsParts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured.ResultsPatients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria.ConclusionThese data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1296-4) contains supplementary material, which is available to authorized users.

The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen–encoding var genes

“…yoelli were detected in semi-immune than naive mice. This was consistent with our observation that the circulating parasites were older in the uncomplicated than the severe malaria patients because we previously showed that the uncomplicated malaria patients had more immunity to PfEMP1 than the severe malaria patients [ 88 ].…”

“…A transcript incorporating DC5 (DBLδ5-CIDRβ3-DBLβ7-[DBLγ4]) (contig12688) was also up-regulated in severe malaria ( p = 0.0537). DC5 was up-regulated in severe malaria in Africa [ 48 ] and expressed in a cerebral malaria case in Papua New Guinea [ 88 ].…”

Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon

“…Regarding B‐cells, a number of observations clearly demonstrate that B‐cell homeostasis is affected by Plasmodium infection . This can be attributed to the complex biology of the parasites , their antigenic diversity , and their immune‐modulatory molecules . The BAFF/APRIL system plays a variety of roles in immunomodulation, mainly by affecting B cell activation, proliferation, and survival.…”

“…Plasmodium infection [17,18,44,45]. This can be attributed to the complex biology of the parasites [46,47], their antigenic diversity [46][47][48], and their immune-modulatory molecules [49,50]. The BAFF/APRIL system plays a variety of roles in immunomodulation, mainly by affecting B cell activation, proliferation, and survival.…”

Longitudinal analysis of naturally acquired antibodies to PfEMP1 CIDR domain variants and their association with malaria protection

“…Immunity to severe malaria is generally acquired after only one to two severe episodes (24) with naturally acquired antibodies specific for PfEMP1 variants likely playing an important role in clinical protection (25). Antibodies to group A PfEMP1 variants tend to be acquired prior to antibodies to group B and C variants (26) and are associated with protection from severe malaria (27). Similarly, antibodies to EPCR-binding CIDRα1 domains are acquired more rapidly than antibodies to other CIDR domains in areas of high malaria transmission intensity and are boosted by severe malaria but not uncomplicated malaria (28, 29).…”