Karolinska: 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.
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.
Publication:
‘
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.
For further information, please contact:
Professor
Mats Wahlgren
, PhD
Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet
Tel: +46 (0)70-556 12 46
E-mail:
mats.wahlgren@ki.se
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