Study may force re-think on rheumatoid arthritis

WASHINGTON (Reuters) -- People with rheumatoid arthritis, who have long been thought to have overactive immune systems, instead may have exhausted immune systems, researchers said on Tuesday.

"What this study has shown for the first time is that patients with rheumatoid arthritis have prematurely aged immune systems," lead author Dr. Cornelia Weyand, a rheumatologist at the Mayo Clinic in Minnesota, said in a statement.

"Until now we have thought that these patients had overactive immune systems, which is why we have aggressively treated the symptoms of rheumatoid arthritis with medications that suppress the immune system," said Weyand, whose findings were published in the Proceedings of the National Academy of Sciences.

"While this practice offers relief of the painful symptoms, it also puts patients at greater risk for infections and cardiovascular disease -- the two leading causes of death among these patients."

Scientists estimate about 2.1 million Americans have rheumatoid arthritis -- most of them women.

The disease is marked by pain, swelling, stiffness and loss of function in the joints. Patients may also complain of fatigue, occasional fever and a general malaise.

It is classified as an autoimmune disease -- one in which the immune system mistakenly attacks healthy tissue.

Weyand and colleagues studied the immune systems of 51 patients with rheumatoid arthritis and compared them to 47 people of similar age who did not have the condition.

They found that the T-cells -- the immune cells that are programmed to recognize and attack invaders such as bacteria and viruses -- were worn out. "They do not make new T-cells," Weyand said in a telephone interview.

One of the strengths of the human immune system is the large repertoire of so-called memory T-cells, which can recognize hundreds of different strains of cold viruses, streptococcal bacteria and thousands of other microbes.

As people age, this repertoire gets smaller, which is one reason why older people are more at risk from diseases such as influenza and food poisoning.

Weyand's team found that young rheumatoid arthritis patients had many fewer different T-cells than they should have. Patients 20 to 30 years old had a collection of T-cells that looked like they belonged to 50- to 60-year-olds.

And the chromosomes in the cells, which are the structures that carry the genetic material, were frayed. Chromosomes are capped with telomeres, which get a little worn with each cell division. The telomeres in the T-cells were worn away.

Weyand said it appeared the thymus glands in the patients -- where T-cells get their "education" -- were not working properly and too few T-cells were being produced.

"These cells ... lose many of their beneficial functions," she said. "But they also have other functions, which predispose them to cause inflammation."

Weyand said it will take more research to tell for sure, but it was possible that patients' immune systems were overactive early on. "There was a phase when the immune system was very active and reached a state of exhaustion," she said.

This could mean that current rheumatoid arthritis drugs that target the immune system may be missing the boat.

"Yes, in the sense that they cannot go to the root of the problem," Weyand said. "We have gotten so much better at treating the symptoms but we are not much closer to curing the disease."

Weyand said the research has wider implications.

"I think as the American population is aging, we are going to take a deep interest in how the immune system is aging," she said. "We will begin to explore how that process occurs and how it can be counteracted."

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Mayo Clinic Arthritis Center
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Arthritis Foundation Home Page
The Arthritis Research Institute of America

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