We finally understand how the immune system helps cause Type 1 diabetes.
Scientists have taken a big step in better understanding how Type 1
diabetes wreaks havoc on the body, which could lead to novel ways to
both treat and prevent the disease.
It was previously known that the chronic autoimmune disease involves
the immune system attacking four molecules, called autoantigens, in the
pancreas. However, diabetes experts have long speculated that a fifth
molecule must also be under attack — but they hadn’t been able to
identify it until now.
Researchers in the U.K. and Italy have discovered the fifth and final
molecule, called tetraspanin-7. Their work could improve diabetes
prediction and treatment, said Dr. Michael Christie, the
reader in biomedical sciences at the University of Lincoln in England who led the research.
“The discovery that tetraspanin-7 is a major target of immunity in
diabetes now provides us with a complete picture of what the immune
system recognizes in individual patients, will assist in identifying
individuals at risk through detection of antibodies to the protein and
will allow the development of procedures to block the tetraspanin-7
immune response as part of a strategy to prevent the disease,” Christie said.
Diabetes is characterized by
high levels of sugar in the blood. For people with Type 1 diabetes — about
1.25 million children and adults in the U.S., according to the American Diabetes Association — this is because the
body fails to produce any or enough insulin, a hormone that helps to
take sugar from the blood to other parts of the body.
The disease is currently treated with insulin. Those who develop Type
1 diabetes must either inject insulin several times a day for the rest
of their lives or administer it through a pump and constantly monitor
their blood glucose. Yet they’re still at risk of experiencing
complications affecting their eyes, feet, circulation or nervous
system, Christie said.
People with Type 1 diabetes tend to have antibodies in their blood
that are specifically linked to each of the molecules that are attacked
by the immune system. Tests that identify who might be at risk of
developing Type 1 diabetes detect these antibodies — the greater the
number of different antibodies found, the higher the risk may be.
The discovery that tetraspanin-7 is a major target
of immunity in diabetes now provides us with a complete picture of what
the immune system recognizes in individual patients...”
Research leader Dr. Michael Christie
For the research,
published last month in the journal Diabetes,
scientists analyzed blood samples from patients with Type 1 diabetes,
and used the antibodies linked to tetraspanin-7 to identify the
molecule. They also collected some previous data on the properties of
the molecule.
When the researchers were able to bind patients’ antibodies to
tetraspanin-7, they knew they had made a groundbreaking discovery.
“We were surprised that we were finally able to discover the identity
of the target of antibodies in Type 1 diabetes after such a long
period, with many groups worldwide on the hunt for it during this time,”
Christie said. “We almost gave up at one stage — our initial test for
binding of patients’ antibodies to tetraspanin-7 was negative! — but we
then realized that perhaps the test we were using was flawed, so we
tried a different approach which worked nicely.”
The researchers concluded that the five major targets of the immune
system’s response in Type 1 diabetes are insulin, an enzyme called
Glutamate decarboxylase, the proteins IA-2 and Zinc transporter-8, and
of course tetraspanin-7.
The more technically named molecules are largely involved in the secreting or storing of insulin,
BBC News reported.
The research can be used to
better identify people at risk of Type 1 diabetes and later inform the crucial development of therapies, Dr. Emily Burns of
Diabetes UK, the charity that co-funded the study with the Society for Endocrinology, said in a statement.
“In order to prevent Type 1 diabetes, we need to fully understand how
the immune response that damages insulin-producing cells develops in
the first place,” she said. “Dr. Christie’s impressive research is
helping us to do just that.”
