New Clue for Smoking's Impact on Rheumatoid Arthritis

MONDAY, Jan. 9/06 (HealthDay News) -- Researchers have known for years that smokers are more likely to develop rheumatoid arthritis, but Swedish scientists now think they know why: Tobacco use makes it more likely that a rare genetic condition will trigger the body's immune system to attack itself.

The findings don't appear likely to contribute to any immediate new treatments for rheumatoid arthritis, which affects an estimated 2.1 million Americans. Still, the research is important because it provides more insight into what causes the disease, said Dr. John Klippel, president and CEO of the Arthritis Foundation.

The researchers are "putting forth a hypothesis, which is as good as anything I've heard of, and makes sense as to what might be going on, at least in people whose smoking has caused this disease," Klippel added.

Rheumatoid arthritis is caused by inflammation in the joints and may stick around indefinitely, flaring up at certain times.

According to researchers, smoking appears to double the risk that someone will get rheumatoid arthritis. That's not a huge increase, considering the small number of people with the condition, but it's been enough to intrigue scientists.

In the new study, researchers analyzed blood samples from hundreds of Swedish citizens, 930 with early stages of rheumatoid arthritis and 383 without. The study findings appear in the January issue of Arthritis & Rheumatism.

The researchers found that a combination of smoking and a genetic trait often combined to cause rheumatoid arthritis. Smokers who had two copies of HLA-DR shared epitope (SE) genes were 21 times more likely to develop rheumatoid arthritis than non-smokers without the gene.

Klippel said it appears that smoking causes an immune reaction in the lungs in people with the gene, and then the same process happens in the joints, causing inflammation as the body tries to fight off what it considers to be an invader. The immune reaction involves citrulline-modified protein, a kind of protein that's rare in healthy people but common in about two-thirds of people with rheumatoid arthritis.

The inflammation "suddenly becomes chronic, and people have disease that lasts for months or years, or likely the rest of their lives," Klippel said.

"The big message isn't a new one: it's 'Don't smoke,'" said Dr. Peter Gregersen, a professor of medicine and pathology at New York University School of Medicine.

But the study provides much more than the obvious, he said. "It's giving us new insight into a major cause of the disease and how it's likely to develop. If we get insight into the actual mechanism, it offers the promise of developing specific therapies."