Scientists Have Solved A Major Diabetes Mystery

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.”