Immune system clues

Understanding cold virus protein may help transplant patients

January 19, 2007|By Dennis O'Brien | Dennis O'Brien,Sun reporter

We all know how our bodies react to a cold - runny nose, stuffed sinuses, watery eyes and so on. And eventually, to our relief, these symptoms disappear.

How all this happens became clearer this week in a report by researchers at the Johns Hopkins University looking for ways to help control the immune systems of organ transplant patients.

Their findings, published yesterday in the journal Nature, show that a typical cold virus produces a protein in your blood that eventually shuts down part of the immune system, drying up the runny nose and sniffles that make life miserable.

The protein, named carabin, was discovered in the early 1990s. But only now have scientists figured out how it works.

"What we've found is it plays a general role of a brake, of sorts, on the immune system," said Jun O. Liu, a professor of pharmacology and neuroscience at the Hopkins medical school.

Without such brakes, your immune system could continue producing cold symptoms or go into overdrive - resulting in an autoimmune disease such as lupus, rheumatoid arthritis or diabetes.

"Anytime you activate the immune system, you run the risk of having it go out of control," said Thomas Tedder, chairman of immunology at the Duke University Medical Center, who was not involved in the study. "You need these regulatory pathways to prevent that."

The work is aimed at increasing what researchers know about our immune systems - and ultimately making life easier for organ transplant recipients, who often develop complications from drugs that suppress their immune systems.

Experts say thousands of transplant patients are living longer each year but face side effects from the immunosuppressant drugs that keep them alive.

"Anything we can do to have the immune system control itself, the better off we are," said Dr. Matt Cooper, a member of the organ transplant team at the University of Maryland Medical Center who was not involved in the study.

The report shows that carabin acts the same way as immunosuppressant drugs now on the market - inhibiting a pathway that activates the immune system, Cooper said.

Researchers have known for years that white blood cells play a key role in our immune systems, producing proteins that attack infections and kill them off. The problem with transplants is that the immune system recognizes the new tissues as foreign and attacks them.

"Your immune system is walking a tight rope between fighting off an infection and causing too many problems," said Cooper, an associate professor of surgery at the University of Maryland School of Medicine.

The first successful organ transplant was performed in Boston in 1954, when Ronald Herrick donated a kidney to his twin brother, Richard, who was dying of kidney disease.

According to the National Kidney Foundation, Richard survived for eight years and the surgeon who performed the transplant, Dr. Joseph Murray, won a Nobel Prize for medicine in 1990.

But organ transplants remained experimental until the 1980s and the advent of cyclosporine, an immunosuppressant that helped patients cope with new organs by preventing their immune systems from responding as if the organs were infections.

Each year, doctors transplant upwards of 25,000 kidneys, livers, hearts, lungs, livers and pancreases, experts say.

"The impact of the immunosuppressant drugs were what made transplants possible," said Cooper, part of a team that performed 330 organ transplants last year at the UM Medical Center.

Some transplant patients can be weaned off immunosuppressants, but most take them for the rest of their lives. "You may hear about the exceptions, but for the most part, it means a life time of medications," Cooper said.

But side effects include tremors, diabetes, kidney failure and weakened immune systems that can turn common infections into deadly threats, experts say.

Liu studies the mechanisms immunosuppressant drugs use to shut down the immune system. His goal is finding immunosuppressants with fewer side effects.

"We're looking for better immunosuppressive drugs, but to be honest, that goal is probably a long, long way down the road," he said.

For the Nature study, Liu and his team added carabin to mouse and human white blood cells that had already been manipulated to fight off infections. The study cost just under $500,000 and is the result of about eight years of work, Liu said.

He found that adding carabin deactivated the blood cells programmed to fight off viral infections, and the more carabin he added, the less active the cells became.

Carabin levels usually reached maximum concentrations in the lab and began shutting off the immune system after about 12 hours, he said. In real life it often takes longer to fight off cold symptoms because of the tenacity of the virus and other factors, he said.

Liu has been working with carabin since the early 1990s and suspected that it played a key role in the immune system response.

"What carabin does is, it takes time to build up and allows the immune system to do it's job, then it turns the system off, so to speak," he said.

Carabin isn't our immune system's only shut-off valve, experts say. But much about the immune system remains a mystery, so identifying any shutoff valves could lead to better medications, they say.

"We're still uncovering all the stones and seeing what's underneath, and this was a basic stone to uncover," Tedder said. "It's a great basic science discovery."

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