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Cytoadherence and rosetting contribute to the development of severe Plasmodium falciparum malaria. In Brazil, severe falciparum malaria is mostly associated with renal or pulmonary complications and very rarely with cerebral malaria. The most N-terminal DBL1α domain of PfEMP1, a protein encoded by the var multi-gene family mediates rosetting. We analyzed parasites of Brazilian patients with severe malaria to determine whether there were particular DBL1α var sequences predominantly expressed in such patients. DBL1α var sequences were obtained from parasites of Brazilian patients with severe and mild malaria and were analyzed by standard bioinformatic programs. Three hundred twenty var DBL1α sequences obtained from 80 Brazilian patients with mild malaria were spotted in high-density filters and hybridized to probes representing predominantly expressed sequences in parasites from patients with severe malaria. A DBL1α domain was expressed in bacteria and used to demonstrate its binding capacity to erythrocytes by immunofluorescence. Forty-three different and unreported DBL1α amino acid sequences were obtained. Sequences predominantly expressed in patients with severe malaria could be subgrouped due to deletions of 1–2-cysteine residues. These sequences were commonly found in the var gene repertoire of parasites from patients with mild malaria, yet they were rarely expressed in these patients. A recombinant protein representing the most abundantly expressed sequence detected in one patient with severe malaria bound directly to uninfected erythrocytes. This is the first report showing an association of severe noncerebral malaria from Brazil with particular DBL1α sequences.
Kirchgatter et al. (Tue,) studied this question.