It has long been known that people with blood type O
are protected from dying of severe malaria. In a
study published in Nature Medicine, a team of
Scandinavian scientists explains the mechanisms
behind the protection that blood type O provides,
and suggest that the selective pressure imposed by
malaria may contribute to the variable global
distribution of ABO blood groups in the human
population.
Anopheles albimanus mosquito. Credit: James Gathany (Wikimedia Commons).
Malaria is a serious disease that is estimated by
the WHO to infect 200 million people a year, 600,000
of whom, primarily children under five, fatally.
Malaria, which is most endemic in sub-Saharan
Africa, is caused by different kinds of parasites
from the plasmodium family, and effectively all
cases of severe or fatal malaria come from the
species known as Plasmodium falciparum. In severe
cases of the disease, the infected red blood cells
adhere excessively in the microvasculature and block
the blood flow, causing oxygen deficiency and tissue
damage that can lead to coma, brain damage and,
eventually death.
Scientists have therefore been keen to learn more
about how this species of parasite makes the
infected red blood cells so sticky.
It has long been known that people with blood type O
are protected against severe malaria, while those
with other types, such as A, often fall into a coma
and die. Unpacking the mechanisms behind this has
been one of the main goals of malaria research.
A team of scientists led from Karolinska Institutet
in Sweden have now identified a new and important
piece of the puzzle by describing the key part
played by the RIFIN protein. Using data from
different kinds of experiment on cell cultures and
animals, they show how the Plasmodium falciparum
parasite secretes RIFIN, and how the protein makes
its way to the surface of the blood cell, where it
acts like glue. The team also demonstrates how it
bonds strongly with the surface of type A blood
cells, but only weakly to type O.
Principal investigator Mats Wahlgren, a Professor at
Karolinska Institutet’s Department of Microbiology,
Tumour and Cell Biology, describes the finding as
“conceptually simple”. However, since RIFIN is found
in many different variants, it has taken the
research team a lot of time to isolate exactly which
variant is responsible for this mechanism.
“Our study ties together previous findings”, said
Professor Wahlgren. “We can explain the mechanism
behind the protection that blood group O provides
against severe malaria, which can, in turn, explain
why the blood type is so common in the areas where
malaria is common. In Nigeria, for instance, more
than half of the population belongs to blood group
O, which protects against malaria.”
The study was financed by grants from the Swedish
Foundation for Strategic Research, the EU, the
Swedish Research Council, the Torsten and Ragnar
Söderberg Foundation, the Royal Swedish Academy of
Sciences, and Karolinska Institutet. Except
Karolinska Institutet, co-authors of the study are
affiliated to Stockholm University, Lund University,
Karolinska University Hospital, and the national
research facility SciLifeLab in Sweden, and to the
University of Copenhagen in Denmark and University
of Helsinki in Finland. Mats Wahlgren is a
shareholder and board member of drug company
Dilaforette AB, which is working on an anti-malaria
drug. The company was founded with support from
Karolinska Development AB, which helps innovators
with patent-protected discoveries reach the
commercial market.
For more information
RIFINs are Adhesins Implicated in Severe Plasmodium
falciparum Malaria
Suchi Goel, Mia Palmkvist, Kirsten Moll, Nicolas
Joannin, Patricia Lara, Reetesh Akhouri, Nasim
Moradi, Karin Öjemalm, Mattias Westman, Davide Angeletti, Hanna Kjellin, Janne Lehtiö, Ola Blixt,
Lars Ideström, Carl G Gahmberg, Jill R Storry,
Annika K. Hult, Martin L. Olsson, Gunnar von Heijne,
IngMarie Nilsson and Mats Wahlgren
Nature Medicine, AOP 9 March 2015, doi:
10.1038/nm.3812
Link...
Karolinska Institutet
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