A protein produced by some strains of the malaria parasite can cause red blood cells, especially in blood group A individuals, to form clumps, thereby increasing the severity of disease, according to research just published.
When certain strains of Plasmodium falciparum , the single-celled parasite that is responsible for the most dangerous forms of malaria, get into red blood cells, those cells start sticking to other red blood cells as well as to walls of blood vessels. The resulting obstruction to blood flow can damage tissues and lead to severe malaria that is life-threatening.
Previous research had implicated the ‘ P. falciparum erythrocyte membrane protein 1’ (PfEMP1) in red blood cells forming clumps. (Such clumps are called ‘rosettes’). Once the parasite infects red blood cells, this protein that it produces appears on the outer surface of those cells. The protein then latches on to receptor molecules found on other red blood cells, creating rosettes.
However, when PfEMP1 was removed from red blood cell surfaces using enzymes, rosette-formation was reduced only in those of blood group O but not blood group A. This indicated that PfEMP1 may not be the only molecule involved in rosette formation, noted a Scandinavian team of scientists in a Nature Medicine paper.
With a series of experiments, the team showed that another protein could have a hand too, principally affecting individuals of blood group A.
The RIFINs too are secreted by the parasite and then get to the surface of red blood cells. There are 150 rif genes that carry the genetic information for RIFINs. One P. falciparum parasite examined by the team carried 85 such genes, but with just one of those genes being responsible for much of the RIFINs it produced.
The RIFINs were thought to act as decoys, making it difficult for the human immune system to detect and destroy parasite-infected red blood cells, commented G. Padmanabhan of the Indian Institute of Science in Bangalore, who has studied the malaria parasite over many decades but was not involved in the research that led to the Nature Medicine paper.
“For the first time another role has been found for the rif gene family,” he told this correspondent.
Suchi Goel of Karolinska Institutet at Stockholm in Sweden and colleagues introduced a rif gene into Chinese hamster ovary cells. Those cells, with the RIFIN protein on their surface, “bound large numbers of group A RBCs [red blood cells],” the scientists noted in their paper. The rosette formation with group O RBCs was “less pronounced.” Moreover, when molecular tags that marked RBCs as belonging to group A were removed, their binding to cells bearing RIFIN were similar to those of group O.
Only RIFINs of sub-group A, which accounts for about 70 per cent of these proteins, led to rosettes being formed.
The protection offered by blood group O could “explain why the blood type is so common in the areas where malaria is common,” said Mats Wahlgren, the study's principal investigator, in a press release.
