Download Singapore Scientists Discover Genetic Link in Kawasaki Disease

RESEARCH
FINDINGS
Singapore Scientists Discover Genetic Link in Kawasaki Disease
S
cientists at the Infectious Diseases
department of the Genome Institute
of Singapore (GIS), an institute of the
Agency for Science, Technology and Research
(A*STAR), led a genome-wide association
study (GWAS) on a world-wide collaboration
on Kawasaki disease. The study, published
in Nature Genetics on 13 November 2011,
indicates that the gene FCGR2A is associated
with an increased risk of contracting the
disease.
The world-wide investigation, linking
five separate consortia, was initiated by GIS,
which was responsible for the study design
and coordination, as well as the laboratory
work and data analysis of samples collected
by its research partners. The study examined
the genetic profiles of 405 children with
Kawasaki disease and contrasted them with
6,252 healthy controls, in Europe, USA and
Australia. Genetic markers showing potential
association with the disease were re-assessed
and validated in a further 740 affected
families, as well as a further 1,028 affected
children and 1,512 healthy controls from
Asian countries.
From the study, the scientists noted very
strong evidence of increased risk of disease
at a gene encoding a protein called FCGR2A.
This protein is well known to Kawasaki
disease doctors because it is a receptor for
intravenous immunoglobulin (IVIG), which is
used for the treatment of Kawasaki disease.
Their observation highlights the importance
of such receptors in the pathogenesis of this
inflammatory disease, and thereby provides
a biological basis for the use of IVIG for
Kawasaki disease treatment. Until now,
researchers were unclear as to how or why
the infusion of IVIG worked in treating the
disease.
Co-lead author of the paper, Senior
Group Leader and Associate Director for
Infectious Diseases at the GIS, Dr Martin
Hibberd said, “The cause and events that
lead to Kawasaki disease have been difficult
mysteries, that are now starting to be
revealed, but only because of world-wide
efforts such as this.Now we have added a very
significant jigsaw piece to the big picture,
I hope we can start to impact on patients
through the development of early diagnosis
and new therapeutic approaches.”
Dr Khor Chiea Chuen, co-first author
and Research Scientist at the GIS added, “I
saw my first patient with Kawasaki disease
as a fourth year medical student five years
ago, and when asked by the child’s parents
regarding the cause of the disease, I didn’t
know much apart from the observation that
Kawasaki disease could be triggered by an
infectious episode. Now, we know more.
We plan to extend this study to involve
Singaporean patients in the near future.”
Kawasaki disease is an autoimmune
disease in which patient’s blood vessels
throughout the body become inflamed. It
affects mostly children, causing prolonged
fever of usually more than five days. It
is unresponsive to antibiotics and antipyrectics, such as paracetomol and aspirin. A
very visible rash develops, and the child is in
obvious discomfort, but it cannot be relieved
by traditional means. Furthermore, there are
other conditions, such as scarlet fever and
measles, which can mimic it, and thus delay
its diagnosis. Early diagnosis is important, so
that IVIG can be administered straightaway.
If IVIG is delayed, there is a significant risk
of irreversible heart damage.
Stem Cells Engineered to Kill Cancer
U
.S. researchers say they’ve shown that
blood stem cells can be engineered to
create cancer-killing T-cells that seek
out and attack a human melanoma.
Jerome Zack -- a scientist with the
University of California, Los Angeles, Jonsson
Comprehensive Cancer Center and the Eli
and Edythe Broad Center of Regenerative
Medicine and Stem Cell Research -- said the
tests, conducted on mice, prove blood stem
cells can be genetically altered in a living
organism to fight cancer.
“We knew from previous studies that we
could generate engineered T-cells, but would
they work to fight cancer in a relevant model
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of human disease, such as melanoma,” Zack
said Tuesday in a release.
In four of the nine mice studied,
the antigen-expressing melanomas were
eliminated. In the other five mice, the
antigen-expressing melanomas decreased
in size.
Researcher Dimitrios Vatakis said the
approach turned a few engineered stem cells
into an army of T-cells that responded to the
presence of the melanoma antigen.
“These cells can exist in the periphery
of the blood and if they detect the melanoma
antigen, they can replicate to fight the
cancer,” he said.
The study appeared in the early online
edition of the Proceedings of the National
Academy of Sciences.