UCI Research Points to Link in Diseases, Treatments
UC Irvine researchers have discovered the first molecular marker linking diabetes, lupus and multiple sclerosis, a finding that may make it possible to treat or arrest human diseases in which the immune system turns on itself.
In an article published today in the European Journal of Immunology, UCI researchers said diseased mice were found to have unusually high numbers of abnormal potassium channels in a particular class of immune cells known as “double-negative” T-cells. These abnormal cells appeared to trigger other immune cells to attack and destroy body tissues, a classic symptom of autoimmune diseases, said Dr. K. George Chandy, one of three researchers at UCI’s department of physiology and biophysics who wrote the article.
If this proves true for humans, it may be possible to develop a single drug to block the abnormal potassium channels and thus control or halt autoimmune diseases, such as juvenile diabetes, lupus, multiple sclerosis, rheumatoid arthritis and myasthenia gravis, which together affect 150 million to 200 million people worldwide, Chandy said.
To that end, the Connecticut-based pharmaceutical firm Pfizer Inc. has awarded the UCI team a $1.5-million, two-year grant to verify that the findings are applicable to humans and to clone the specific potassium channel gene, which could help in designing such a drug.
“We do not know yet whether this is a result of a disease or contributes to the disease process,” said Chandy, an assistant professor who heads up the project with Stephan Grissmer, a post-doctoral researcher, and Michael Cahalan, professor of physiology and biophysics.
“What we believe might be happening is that these (abnormal) cells stimulate other cells to destroy the immune system,” said Chandy, who also works in the School of Medicine’s division of rheumatology and clinical immunology.
Potassium channels, the focus of the UCI team’s research, are proteins on cell surfaces that allow potassium ions to enter or leave a cell. There are many different types of potassium channels in the body, and they work to regulate the nervous system and the heart. Drugs that regulate other types of potassium channels already are in wide use to treat high blood pressure and irregular heartbeats and may also prove effective for asthma.
“This research has two profound implications,” said Dr. Peng Thim Fan, a rheumatologist/immunologist and chairman of the medical and scientific committee of the Southern California chapter of the Arthritis Foundation in Los Angeles.
“The first is that it gives us a means of further studying and identifying what exactly goes wrong in the disease process,” Fan said. “In other words, why are we reacting against our own tissue? Secondly, it allows us to develop new drugs or medications that may either reverse this abnormality or block it, which means that we may be much closer to a potential cure for these diseases.
“The only way now to treat arthritis is to give drugs that may slow down the process or treat specific symptoms. But we don’t really have anything that stops the diseases from happening.”
Dr. David Wofsy, a professor at the UC San Francisco Medical Center and physician at the Veterans Administration Hospital’s arthritis center, called the UCI team’s findings “an important contribution” in understanding how autoimmune diseases work.
In test mice with juvenile diabetes, systemic lupus erythematosus and a model for multiple sclerosis, the UCI team examined the “double-negative” T-cells and found that a particular type of potassium channel in the cells jumps in number from about 10 to 200 with the onset of the diseases.
“The only time we see this particular molecule is in (mice with) autoimmune disease,” Chandy said.
Double-negative T-cells account for less than 5% of the body’s millions of lymphocytes, a class of blood cells that attack viruses and other diseases. Their normal function is not well understood. But these cells have been given increasing scrutiny for their possible role in autoimmune diseases, Chandy said.
