BACKGROUND: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens play an important role in host immune system evasion and parasite sequestration. The PfEMP1 antigenic domains that drive immune-mediated protection from severe malaria have not been identified. We hypothesized that Malian children with severe malaria lack serorecognition to distinct subsets of PfEMP1s compared with matched uncomplicated malaria controls. METHODS: We developed a custom protein microarray including 79 fragments from PfEMP1s associated with severe malaria, including domain cassettes (DCs) 1, 4, 5, 8, 13, and 15, from reference and sequenced Malian field isolates. We measured serological responses for cases of cerebral malaria (CM), severe malarial anemia (SMA), concurrent CM with SMA, and age-matched controls with uncomplicated malaria. RESULTS: Malian children with severe malaria had distinct gaps in antibodies to PfEMP1 subtypes, including DCs 1, 8, and 13 for SMA and DC13 for CM. Few PfEMP1 DCs were differentially seroreactive, but seroreactivity to domain couplets downstream from these DCs differed. CONCLUSIONS: The presence of antibodies directed at downstream PfEMP1 domains may reflect severe malaria exposure but could also be a focus of protective natural immunity to severe malaria. Future studies should examine antibody responses to sequenced PfEMP1s from severe malaria infections to precisely ascertain immune gaps.
Travassos et al. (Thu,) studied this question.